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Oregon State University
1.
Kyrylkova, Kateryna.
The role of the transcriptional regulatory protein BCL11B in dental and craniofacial development.
Degree: PhD, Pharmacy, 2014, Oregon State University
URL: http://hdl.handle.net/1957/45238 
► BCL11B is a transcriptional regulatory protein that plays essential roles during mouse embryonic development. BCL11B is expressed and functions in the immune and nervous systems…
(more)
▼ BCL11B is a transcriptional regulatory protein that plays essential roles during mouse embryonic development. BCL11B is expressed and functions in the immune and nervous systems as well as within ectodermal organs. Multiple studies have characterized the roles of BCL11B in T cells, brain, and skin. However, very little is known about the mechanistic role of BCL11B during tooth development, and data are not available on the function of BCL11B in the craniofacial skeleton.
BCL11B is expressed widely within the oral cavity during development, and mice lacking BCL11B exhibit a spectrum of tooth developmental defects. The most striking feature of the Bcl11b[superscript -/-] dental phenotype is a defect in development of enamel-secreting cells, known as ameloblasts, in the mouse incisor. Ameloblasts are localized exclusively on the labial aspect of the mouse incisor in wild-type mice. In contrast, Bcl11b[superscript -/-] mice exhibit defective ameloblasts on the labial and develop ectopic, ameloblast-like cells on the lingual aspect of the tooth. BCL11B regulates asymmetric ameloblast formation by regulating the development of epithelial stem cell niches in the posterior part of the incisor. Specifically, BCL11B induces proliferation and differentiation of epithelial stem cells into ameloblasts in the labial cervical loop, whereas BCL11B suppresses these processes within the lingual epithelium. Such bidirectional actions of BCL11B are mediated by spatio-specific regulation of a large gene network comprised of genes that encode members of fibroblast growth factor (FGF) and transforming growth factor β (TGFβ) superfamilies, Sprouty proteins, and sonic hedgehog (SHH). In addition, my data integrate BCL11B into FGF and SHH signaling pathways revealing the molecular mechanisms that suppress development of ectopic ameloblast-like cells in the lingual epithelium. In the second half of this dissertation, I show that BCL11B is expressed in the osteogenic mesenchyme of developing craniofacial skeleton, and loss of BCL11B in these tissues has striking effects on craniofacial development. Bcl11b[superscript -/-] mice exhibit accelerated mineralization of the skull during embryonic development and synostosis of facial and coronal sutures. My results demonstrate that BCL11B normally functions to suppress proliferation and premature differentiation of osteoblasts in the craniofacial complex. I suggest that the principal mechanistic basis of these actions of BCL11B is the repression of Fgfr2c expression within the osteogenic mesenchyme. Taken together, my data demonstrate that BCL11B plays an important role in proliferation and differentiation of ameloblast and osteoblast lineages. In addition, my work implicates BCL11B in regulation of FGF and TGFβ signaling pathways. Therefore, these studies contribute to a better understanding of the molecular and cellular functions of BCL11B in vivo.
Advisors/Committee Members: Leid, Mark (advisor), Kioussi, Chrissa (committee member).
Subjects/Keywords: Transcription factor; Transcription factors
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APA (6th Edition):
Kyrylkova, K. (2014). The role of the transcriptional regulatory protein BCL11B in dental and craniofacial development. (Doctoral Dissertation). Oregon State University. Retrieved from http://hdl.handle.net/1957/45238
Chicago Manual of Style (16th Edition):
Kyrylkova, Kateryna. “The role of the transcriptional regulatory protein BCL11B in dental and craniofacial development.” 2014. Doctoral Dissertation, Oregon State University. Accessed February 23, 2020.
http://hdl.handle.net/1957/45238.
MLA Handbook (7th Edition):
Kyrylkova, Kateryna. “The role of the transcriptional regulatory protein BCL11B in dental and craniofacial development.” 2014. Web. 23 Feb 2020.
Vancouver:
Kyrylkova K. The role of the transcriptional regulatory protein BCL11B in dental and craniofacial development. [Internet] [Doctoral dissertation]. Oregon State University; 2014. [cited 2020 Feb 23].
Available from: http://hdl.handle.net/1957/45238.
Council of Science Editors:
Kyrylkova K. The role of the transcriptional regulatory protein BCL11B in dental and craniofacial development. [Doctoral Dissertation]. Oregon State University; 2014. Available from: http://hdl.handle.net/1957/45238
2.
Palagi, Alexandre.
Découverte et analyse d’inactivateurs de transcription chez la Drosophile agissant comme amplificateurs dans différents contextes cellulaires : Discovery and analysis of silencers in Drosophila acting as enhancers in other cellular contexts.
Degree: Docteur es, Interactions moléculaires et cellulaires, 2018, Côte d'Azur
URL: http://www.theses.fr/2018AZUR4006
► Un des enjeux majeurs de la biologie moderne est de comprendre les mécanismes complexes régissant l’expression de gènes d’un organisme en développement. Alors que les…
(more)
▼ Un des enjeux majeurs de la biologie moderne est de comprendre les mécanismes complexes régissant l’expression de gènes d’un organisme en développement. Alors que les activateurs (enhancers) ont été abondamment étudiés et analysés, seul un relatif petit nombre de répresseurs (silencers) a été identifié à ce jour et restent jusqu’à présent assez mal compris. Un nombre non négligeable de CRMs jouent par ailleurs un double rôle à la fois d’amplificateurs et d’inactivateurs de transcription en fonction de l’état ou du type cellulaire dans lequel ils se trouvent, rajoutant un niveau supplémentaire de à la régulation génique dans différents types cellulaires et tissus. De façon surprenante, nous avons découvert que tous les éléments ayant une activité de répression transcriptionnelle que nous avons identifiés, s’avèrent aussi avoir une activité d’activation transcriptionnelle dans d’autres contextes cellulaires. Nos résultats remettent donc en question le paradigme de deux catégories distinctes de CRMs et suggèrent que des milliers, ou plus, d’éléments bifonctionnels restent à être découverts chez la Drosophile et potentiellement 104-105 chez l’humain. Le référencement et la caractérisation de ces éléments devraient s’avérer utiles, si ce n’est cruciaux, afin de comprendre la façon par laquelle ces motifs d’expression sont encodés au sein des génomes d'organismes métazoaires et donc éventuellement chez l’Homme.
A major challenge in biology is to understand how complex gene expression patterns in organismal development are encoded in the genome. While transcriptional enhancers have been studied extensively, few transcriptional silencers have been identified and they remain poorly understood. Here we used a novel strategy to screen hundreds of sequences for tissue-specific silencer activity in whole Drosophila embryos. Strikingly, 100% of the tested elements that we found to act as transcriptional silencers were also active enhancers in other cellular contexts. These elements were enriched in highly occupied target (HOT) region overlap (Roy et al., 2010) and specific transcription factor (TF) motif combinations. CRM bifunctionality complicates the understanding of how gene regulation is specified in the genome and how it is read out differently in different cell types. Our results challenge the common practice of treating elements with enhancer activity identified in one cell type as serving exclusively activating roles in the organism and suggest that thousands or more bifunctional CRMs remain to be discovered in Drosophila and perhaps 104-105 in human (Heintzman et al., 2009). Characterization of bifunctional elements should aid in investigations of how precise gene expression patterns are encoded in the genome.
Advisors/Committee Members: Bulyk, Martha L. (thesis director), Luton, Frédéric (thesis director).
Subjects/Keywords: Répresseurs; Transcription; Silencers; Transcription
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APA (6th Edition):
Palagi, A. (2018). Découverte et analyse d’inactivateurs de transcription chez la Drosophile agissant comme amplificateurs dans différents contextes cellulaires : Discovery and analysis of silencers in Drosophila acting as enhancers in other cellular contexts. (Doctoral Dissertation). Côte d'Azur. Retrieved from http://www.theses.fr/2018AZUR4006
Chicago Manual of Style (16th Edition):
Palagi, Alexandre. “Découverte et analyse d’inactivateurs de transcription chez la Drosophile agissant comme amplificateurs dans différents contextes cellulaires : Discovery and analysis of silencers in Drosophila acting as enhancers in other cellular contexts.” 2018. Doctoral Dissertation, Côte d'Azur. Accessed February 23, 2020.
http://www.theses.fr/2018AZUR4006.
MLA Handbook (7th Edition):
Palagi, Alexandre. “Découverte et analyse d’inactivateurs de transcription chez la Drosophile agissant comme amplificateurs dans différents contextes cellulaires : Discovery and analysis of silencers in Drosophila acting as enhancers in other cellular contexts.” 2018. Web. 23 Feb 2020.
Vancouver:
Palagi A. Découverte et analyse d’inactivateurs de transcription chez la Drosophile agissant comme amplificateurs dans différents contextes cellulaires : Discovery and analysis of silencers in Drosophila acting as enhancers in other cellular contexts. [Internet] [Doctoral dissertation]. Côte d'Azur; 2018. [cited 2020 Feb 23].
Available from: http://www.theses.fr/2018AZUR4006.
Council of Science Editors:
Palagi A. Découverte et analyse d’inactivateurs de transcription chez la Drosophile agissant comme amplificateurs dans différents contextes cellulaires : Discovery and analysis of silencers in Drosophila acting as enhancers in other cellular contexts. [Doctoral Dissertation]. Côte d'Azur; 2018. Available from: http://www.theses.fr/2018AZUR4006
University of Utah
3.
Close, Devin W.
Structural and Biochemical Studies of the Transcription Elongation Factors Spt6 and Tex.
Degree: PhD, Biochemistry;, 2010, University of Utah
URL: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/719/rec/1086
► Proper gene expression relies on the precise coordination of cellular processes that influence packaging, transcription, and processing of the genetic material. Linkage and regulation of…
(more)
▼ Proper gene expression relies on the precise coordination of cellular processes that influence packaging, transcription, and processing of the genetic material. Linkage and regulation of these processes is organized by factors that remodel and modify nucleosomes, regulate transcription, and influence RNA processing and export. One of these factors, Spt6, is a large (~168kDa), essential, highly conserved, and functionally diverse eukaryotic protein. Best known as a histone chaperone capable of altering the structure of nucleosomes, Spt6 has also been shown to function as a transcription elongation factor as well as a critical component for proper RNA processing. Although a broader role for Spt6 is reasonably well-understood, very little is known about the functional and mechanistic details of this multifaceted protein. Beyond studying Spt6 directly, insight into Spt6 function may come from complimentary studies on the bacterial protein Tex. Tex is a transcription elongation factor predicted to be a structurally similar to Spt6. The function of Tex is not well-understood, but may be functioning in a homologous manner to Spt6 in two vastly different transcriptional environments. In order to gain insight into the mechanism of Spt6 and Tex, the work presented in this thesis has focused on structural and biochemical studies of Spt6 from Saccharomyces cerevisiae and the related Tex protein from Pseudomonas aeruginosa. To this end, several Spt6 crystal structures have been determined resulting in a nearly complete composite model for Spt6. Along with a series of domains predicted to mediate protein and nucleic acid interactions, the structure reveals a novel tandem SH2 domain consisting of the only two SH2 folds known in yeast. Biochemical analysis of Spt6 demonstrates its capacity to interact with an array of functionally relevant protein and nucleic acid substrates which provide clues into mechanisms underlying the various functions of Spt6. Parallel studies on Tex demonstrate a strikingly similar structure and domain architecture to that of the Spt6 core. Structural and biochemical work described in this thesis lays the foundation for further in vitro and in vivo studies aimed at a better understanding of how Spt6 and Tex regulate gene expression. The highly similar core structure shared between Spt6 and Tex may ultimately prove to be a protein scaffold for regulating transcription in both eukaryotic and prokaryotic organisms.
Subjects/Keywords: Transcription Factors
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APA (6th Edition):
Close, D. W. (2010). Structural and Biochemical Studies of the Transcription Elongation Factors Spt6 and Tex. (Doctoral Dissertation). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/719/rec/1086
Chicago Manual of Style (16th Edition):
Close, Devin W. “Structural and Biochemical Studies of the Transcription Elongation Factors Spt6 and Tex.” 2010. Doctoral Dissertation, University of Utah. Accessed February 23, 2020.
http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/719/rec/1086.
MLA Handbook (7th Edition):
Close, Devin W. “Structural and Biochemical Studies of the Transcription Elongation Factors Spt6 and Tex.” 2010. Web. 23 Feb 2020.
Vancouver:
Close DW. Structural and Biochemical Studies of the Transcription Elongation Factors Spt6 and Tex. [Internet] [Doctoral dissertation]. University of Utah; 2010. [cited 2020 Feb 23].
Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/719/rec/1086.
Council of Science Editors:
Close DW. Structural and Biochemical Studies of the Transcription Elongation Factors Spt6 and Tex. [Doctoral Dissertation]. University of Utah; 2010. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/719/rec/1086
University of Georgia
4.
Jones, Tamara Nicole.
Biochemical investigation of protein/protein interactions involving acid-rich domains from transcription factors.
Degree: MS, Biochemistry and Molecular Biology, 2004, University of Georgia
URL: http://purl.galileo.usg.edu/uga_etd/jones_tamara_n_200405_ms
► In eukaryotic cells, transcription is regulated through a complex network of macromolecular interactions mediated by transcription factors, coactivators, and corepressors. To better understand how this…
(more)
▼ In eukaryotic cells,
transcription is regulated through a complex network of macromolecular interactions mediated by
transcription factors, coactivators, and corepressors. To better understand how this network governs gene expression, it is critical to understand the precise details of the macromolecular interactions involved. The tumor suppressor protein p53 interacts specifically with several components of the general
transcription machinery as well as numerous other cellular proteins. In the research presented here, nuclear magnetic resonance (NMR) and in vitro binding assays were used to examine the interaction between p53 and the cellular
transcription factors TFIIH, CBP, and GATA. We have determined that p53 can bind to these three
transcription factors through its amino-terminal acidic activation domain (AAD). Although all these factors bind to the same domain, it seems that they are each able to recognize distinct amino acids within the domain. Precise details like these are critical if we are to understand the intricacies of the
transcription process.
Advisors/Committee Members: James Omichinski.
Subjects/Keywords: transcription
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APA (6th Edition):
Jones, T. N. (2004). Biochemical investigation of protein/protein interactions involving acid-rich domains from transcription factors. (Masters Thesis). University of Georgia. Retrieved from http://purl.galileo.usg.edu/uga_etd/jones_tamara_n_200405_ms
Chicago Manual of Style (16th Edition):
Jones, Tamara Nicole. “Biochemical investigation of protein/protein interactions involving acid-rich domains from transcription factors.” 2004. Masters Thesis, University of Georgia. Accessed February 23, 2020.
http://purl.galileo.usg.edu/uga_etd/jones_tamara_n_200405_ms.
MLA Handbook (7th Edition):
Jones, Tamara Nicole. “Biochemical investigation of protein/protein interactions involving acid-rich domains from transcription factors.” 2004. Web. 23 Feb 2020.
Vancouver:
Jones TN. Biochemical investigation of protein/protein interactions involving acid-rich domains from transcription factors. [Internet] [Masters thesis]. University of Georgia; 2004. [cited 2020 Feb 23].
Available from: http://purl.galileo.usg.edu/uga_etd/jones_tamara_n_200405_ms.
Council of Science Editors:
Jones TN. Biochemical investigation of protein/protein interactions involving acid-rich domains from transcription factors. [Masters Thesis]. University of Georgia; 2004. Available from: http://purl.galileo.usg.edu/uga_etd/jones_tamara_n_200405_ms
Penn State University
5.
Dutta, Arnob.
UNDERSTANDING HOW DHH1 AND CCR4-NOT COMPLEX.
Degree: PhD, Cell and Developmental Biology, 2010, Penn State University
URL: https://etda.libraries.psu.edu/catalog/11126
► The life of mRNA begins with transcription in the nucleus and ends with destruction in the cytoplasm. Several proteins work in unison to regulate the…
(more)
▼ The life of mRNA begins with transcription in the
nucleus and ends with destruction in the cytoplasm. Several
proteins work in unison to regulate the various stages of mRNA
metabolism. The Ccr4-Not complex plays roles from the “birth” to
the “death” of mRNAs. Dhh1, an evolutionarily conserved member of
the DEAD box family in yeast, associates with the Ccr4-Not complex,
and regulates both transcription and mRNA decay. Additionally, in
response to cellular stress, Dhh1 localizes to P-bodies where it
affects the destruction of mRNAs. By interacting with the
translation machinery Dhh1 and its orthologs also play roles in
translational repression. Further it also plays important roles in
G1/S DNA damage checkpoint recovery. Given the many functions of
Dhh1 in both the synthesis and decay of RNAs, this study seeks to
examine the structural requirements for all of Dhh1’s functions.
Biochemical analysis of Dhh1 reveals that this protein binds RNA
with high affinity but displays poor ATPase activity in vitro as
compared to other DEAD box helicases. By studying the biochemical
activities of Dhh1, key residues involved in ATP and RNA binding,
and ATP hydrolysis have been identified. Next, this study helps
dissect out how inactivation of these various biochemical
activities affects the functioning of Dhh1, in vivo. In vivo
analysis of mutant alleles that affect the biochemical activities
has revealed the important roles of ATP binding and hydrolysis in
most of the functions of Dhh1. Interestingly, the weak ATPase
activity of Dhh1 is in part due to extensive inter-domain
interactions, disruption of which greatly enhances ATP hydrolysis.
We hypothesize that Dhh1 activity is stimulated by cellular
factors, which impart a tight regulation on the functioning of this
very abundant helicase. The highly conserved Ccr4-Not complex has
been ascribed many functions, from transcription regulation to mRNA
decay. Initial studies described a role of this complex in
preinitiation complex formation, but a number of studies have
clearly shown Ccr4-Not mediates deadenylation of mRNAs and protein
ubiquitylation in the cytoplasm. It is still not clear how Ccr4-Not
regulates gene expression, and which of these functions are
controlled directly by this complex. This study demonstrates that
Ccr4-Not complex directly regulates RNAP II-dependent transcription
elongation. Using purified Ccr4-Not complex and yeast RNAP II in an
in vitro transcription system, the role of the Ccr4-Not complex in
regulating transcription elongation has been studied. Studies show
that the complex binds directly to the elongating RNAP II complex,
which is partially dependent on the emerging transcript, and it
also makes contacts with the emerging transcript. Using
transcription run on assays, Ccr4-Not is shown to stimulate the
resumption of elongation from paused RNAP II elongation complexes.
Further, Ccr4-Not works co-operatively with positive elongation
factor TFIIS to stimulate elongation through transcription blocks.
The in vitro results are substantiated by in vivo…
Subjects/Keywords: transcription; mRNA
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APA (6th Edition):
Dutta, A. (2010). UNDERSTANDING HOW DHH1 AND CCR4-NOT COMPLEX. (Doctoral Dissertation). Penn State University. Retrieved from https://etda.libraries.psu.edu/catalog/11126
Chicago Manual of Style (16th Edition):
Dutta, Arnob. “UNDERSTANDING HOW DHH1 AND CCR4-NOT COMPLEX.” 2010. Doctoral Dissertation, Penn State University. Accessed February 23, 2020.
https://etda.libraries.psu.edu/catalog/11126.
MLA Handbook (7th Edition):
Dutta, Arnob. “UNDERSTANDING HOW DHH1 AND CCR4-NOT COMPLEX.” 2010. Web. 23 Feb 2020.
Vancouver:
Dutta A. UNDERSTANDING HOW DHH1 AND CCR4-NOT COMPLEX. [Internet] [Doctoral dissertation]. Penn State University; 2010. [cited 2020 Feb 23].
Available from: https://etda.libraries.psu.edu/catalog/11126.
Council of Science Editors:
Dutta A. UNDERSTANDING HOW DHH1 AND CCR4-NOT COMPLEX. [Doctoral Dissertation]. Penn State University; 2010. Available from: https://etda.libraries.psu.edu/catalog/11126
University of Manchester
6.
Gu, Muxin.
Functions of Histone H2A.Z in Regulating Transcript
Levels in Budding Yeast.
Degree: 2016, University of Manchester
URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:305862
► The histone variant H2A.Z is an important regulator of transcription. One unsolved mystery is that why H2A.Z can have both activating and repressive effects on…
(more)
▼ The histone variant H2A.Z is an important regulator
of
transcription. One unsolved mystery is that why H2A.Z can have
both activating and repressive effects on gene expression. By
examining both coding and non-coding RNA transcripts in
S.cerevisiae, we established that H2A.Z is present at both coding
and non-coding promoters and have positive effects on the level of
transcripts. The repressive effect of H2A.Z can be partially
explained by the sense transcripts of gene being antagonised by
H2A.Z-activated antisense transcripts. We also established that
H2A.Z-associated non-coding transcripts are predominantly located
at bidirectional promoters. The sense and antisense pairs produced
from bidirectional promoters show high degrees of coregulation
(especially co-activation) during stress response. Surprisingly, we
found that the non-coding RNA co-activated with stress-response
genes tend to spread the activation signal to the neighbouring gene
further upstream, indicating their potential functions in gene
regulation. In addition, we also observed that accumulation of
H2A.Z at gene promoters is associated with slower recovery from
gene induction, which could be related to the Ino80 pathway. In
general, our results confirmed the interleaved nature of regulatory
system in eukaryotes and highlighted the importance of taking both
coding and non-coding transcripts into account while studying the
transcriptional regulation.
Advisors/Committee Members: RATTRAY, MAGNUS M, SHARROCKS, ANDREW AD, Rattray, Magnus, Sharrocks, Andrew, Millar, Catherine.
Subjects/Keywords: H2A.Z; Transcription
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APA (6th Edition):
Gu, M. (2016). Functions of Histone H2A.Z in Regulating Transcript
Levels in Budding Yeast. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:305862
Chicago Manual of Style (16th Edition):
Gu, Muxin. “Functions of Histone H2A.Z in Regulating Transcript
Levels in Budding Yeast.” 2016. Doctoral Dissertation, University of Manchester. Accessed February 23, 2020.
http://www.manchester.ac.uk/escholar/uk-ac-man-scw:305862.
MLA Handbook (7th Edition):
Gu, Muxin. “Functions of Histone H2A.Z in Regulating Transcript
Levels in Budding Yeast.” 2016. Web. 23 Feb 2020.
Vancouver:
Gu M. Functions of Histone H2A.Z in Regulating Transcript
Levels in Budding Yeast. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2020 Feb 23].
Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:305862.
Council of Science Editors:
Gu M. Functions of Histone H2A.Z in Regulating Transcript
Levels in Budding Yeast. [Doctoral Dissertation]. University of Manchester; 2016. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:305862
Oregon State University
7.
Bhattacharya, Shreya.
Transcription factor CTIP2 regulates hair follicle development, hair cycling and wound healing.
Degree: PhD, Molecular and Cellular
, 2014, Oregon State University
URL: http://hdl.handle.net/1957/50364
► The integumentary system is the largest organ system of the body that comprises of skin and its appendages such as hair follicles, sebaceous and sweat…
(more)
▼ The integumentary system is the largest organ system of the body that comprises of skin and its appendages such as hair follicles, sebaceous and sweat glands. Skin is divided into three distinct structural layers: the epidermis, dermis and hypodermis. The epidermis originates from the ectoderm and is composed of four layers specified as basal, spinous, granular and corneal layer. The function of epidermis is to protect against all sources of environmental insults, prevent water loss and undergo re-epithelialization after wounding. For its normal functioning, the epidermis continually replenishes itself through a process of continuous proliferation and terminal differentiation of keratinocytes from the basal layer.
The hair follicle is a complex appendage of skin, which give rise to the keratinized hair shaft. Hair follicle is formed during embryonic development and it goes through cycles of growth (anagen), regression (catagen) and quiescence (telogen). The bulge region of the hair follicle in the outer root sheath area contains slow-cycling stem cells which are responsible for normal hair cycling as well as cutaneous wound repair after injury.
CTIP2 (COUP-TF interacting protein 2) is a C2H2 zinc finger
transcription factor that is expressed in various organs and tissues. It has been shown to play an important role in the development of thymocyte, tooth and corticospinal motor neuron. Expression of CTIP2 is observed in the developing murine epidermis and dermis during skin organogenesis and predominantly in epidermal keratinocytes in adult mice skin. It is also expressed in the embryonic and mature adult hair follicles, especially in bulge region. CTIP2 regulates epidermal proliferation and terminal differentiation during embryogenesis and adulthood. Here we show that CTIP2 controls hair follicle development, hair cycling and cutaneous wound healing. To study the role of CTIP2 in hair morphogenesis and hair cycling, we have utilized two different genetically modified mouse strains. First, we studied the effect of CTIP2 during hair follicle formation using Ctip2-null mice containing a germline deletion of Ctip2. Ctip2-null mice exhibited reduced hair follicle density and downregulation of EGFR and NOTCH1 expression. To analyze the consequence of loss-of–funtion of CTIP2 on postnatal hair cycling, we selectively ablated Ctip2 in the epidermis and hair follicles using the Cre-LoxP strategy to generate Ctip2[superscript ep-/-] mice. Ctip2[superscript ep-/-] mice showed a defect in postnatal hair cycling marked by early exit from telogen and premature entry into anagen. The premature induction of anagen is a result of stem cell activation, increase in cell proliferation and decrease in apoptosis-driven cell death in the hair follicles. This early activation of follicular stem cells eventually leads to their depletion and therefore ultimate loss of hair follicles and hair coat. Reduced expression of LHX2 and NFATC1, which are two important regulators of hair cycling, was observed in the bulge area of Ctip2[superscript…
Advisors/Committee Members: Indra, Arup K. (advisor), Leid, Mark (committee member).
Subjects/Keywords: Transcription factors
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APA ·
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Manager
APA (6th Edition):
Bhattacharya, S. (2014). Transcription factor CTIP2 regulates hair follicle development, hair cycling and wound healing. (Doctoral Dissertation). Oregon State University. Retrieved from http://hdl.handle.net/1957/50364
Chicago Manual of Style (16th Edition):
Bhattacharya, Shreya. “Transcription factor CTIP2 regulates hair follicle development, hair cycling and wound healing.” 2014. Doctoral Dissertation, Oregon State University. Accessed February 23, 2020.
http://hdl.handle.net/1957/50364.
MLA Handbook (7th Edition):
Bhattacharya, Shreya. “Transcription factor CTIP2 regulates hair follicle development, hair cycling and wound healing.” 2014. Web. 23 Feb 2020.
Vancouver:
Bhattacharya S. Transcription factor CTIP2 regulates hair follicle development, hair cycling and wound healing. [Internet] [Doctoral dissertation]. Oregon State University; 2014. [cited 2020 Feb 23].
Available from: http://hdl.handle.net/1957/50364.
Council of Science Editors:
Bhattacharya S. Transcription factor CTIP2 regulates hair follicle development, hair cycling and wound healing. [Doctoral Dissertation]. Oregon State University; 2014. Available from: http://hdl.handle.net/1957/50364
University of Manitoba
8.
Unger, Mark.
Studying the role of the AdeIJK RND efflux pump and its transcriptional regulator AdeN in the resistance and virulence of Acinetobacter baumannii.
Degree: Microbiology, 2017, University of Manitoba
URL: http://hdl.handle.net/1993/32505
► Acinetobacter baumannii, a Gram-negative bacterium, is a problematic opportunistic pathogen due to its resistance to multiple antibiotics. Energy-dependent efflux of antibiotics mediated by proteins belonging…
(more)
▼ Acinetobacter baumannii, a Gram-negative bacterium, is a problematic opportunistic pathogen due to its resistance to multiple antibiotics. Energy-dependent efflux of antibiotics mediated by proteins belonging to the Resistance-Nodulation-Division (RND) family is the predominant mechanism of intrinsic resistance in A. baumannii. AdeIJK is one such pump that is known to efflux a multitude to antibiotics in A. baumannii. AdeN, a TetR-family protein, has been previously shown to act as a repressor of the AdeIJK efflux pump. However, unlike other RND efflux pump regulators in A. baumannii adeN is not a linked to the adeIJK operon, it is instead located 813kbp upstream of the adeIJK efflux pump-encoding operon. Previous study by our group of the triclosan-resistant mutant AB042, which has a 73bp deletion in adeN, showed changes in the expression of a significant number of genes and proteins, indicating that AdeN may be acting as a global
transcription regulator in A. baumannii. To study the role of AdeN, we have created an unmarked deletion mutant of adeN (AB141) in ATCC17978. Quantitative reverse transcriptase PCR in combination with transcriptomic and proteomic analysis was performed on AB141 to determine if AdeN is acting as a global
transcription regulator. Biofilm formation, motility, virulence, antibiotic susceptibility, and microbial growth were also evaluated to assess the phenotypic effect of adeN deletion on A. baumannii. Transcriptomic and proteomic analysis of AB141 showed that adeN deletion results in differential expression of 106 genes greater than 1.5log(2) fold. Using a proteomics approach, we detected 31 proteins whose expression was altered greater than 1.5 fold. Phenotypic testing led to the observation that deletion of adeN results in decreased susceptibility to antibiotics and osmotic stress. The adeN deletion mutant also exhibited attenuated virulence, decreased biofilm formation and motility. In order to determine if the observed phenotypes were a result of overexpression of AdeIJK rather than loss of AdeN expression, an adeIJK deletion mutant (AB185) and a double mutant of adeN
7
and adeIJK (AB186) were created in ATCC17978 background and phenotypically evaluated alongside the adeN mutant AB141. Intriguingly both adeIJK deletion mutants also exhibited attenuated virulence and motility compared to wild-type. These data indicate that AdeN likely plays a much larger role as a global regulator in A. baumannii with respect to resistance and virulence, however the interactions between AdeN and AdeIJK are much more complicated than originally thought.
Advisors/Committee Members: Kumar, Ayush (Microbiology) (supervisor), Oresnik, Ivan (Microbiology) .
Subjects/Keywords: Transcription Regulation
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APA (6th Edition):
Unger, M. (2017). Studying the role of the AdeIJK RND efflux pump and its transcriptional regulator AdeN in the resistance and virulence of Acinetobacter baumannii. (Masters Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/32505
Chicago Manual of Style (16th Edition):
Unger, Mark. “Studying the role of the AdeIJK RND efflux pump and its transcriptional regulator AdeN in the resistance and virulence of Acinetobacter baumannii.” 2017. Masters Thesis, University of Manitoba. Accessed February 23, 2020.
http://hdl.handle.net/1993/32505.
MLA Handbook (7th Edition):
Unger, Mark. “Studying the role of the AdeIJK RND efflux pump and its transcriptional regulator AdeN in the resistance and virulence of Acinetobacter baumannii.” 2017. Web. 23 Feb 2020.
Vancouver:
Unger M. Studying the role of the AdeIJK RND efflux pump and its transcriptional regulator AdeN in the resistance and virulence of Acinetobacter baumannii. [Internet] [Masters thesis]. University of Manitoba; 2017. [cited 2020 Feb 23].
Available from: http://hdl.handle.net/1993/32505.
Council of Science Editors:
Unger M. Studying the role of the AdeIJK RND efflux pump and its transcriptional regulator AdeN in the resistance and virulence of Acinetobacter baumannii. [Masters Thesis]. University of Manitoba; 2017. Available from: http://hdl.handle.net/1993/32505
Harvard University
9.
Tzeng, Christopher.
Regulation of Synapse Refinement by Visual Experience-Dependent Transcription.
Degree: PhD, 2019, Harvard University
URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029688
► Visual input mediates the structural and functional refinement of synapses in the developing visual system. Proper wiring of this circuitry is dependent on new gene…
(more)
▼ Visual input mediates the structural and functional refinement of synapses in the developing visual system. Proper wiring of this circuitry is dependent on new gene transcription that occurs in the post-synaptic cell following stimulus-evoked neuronal activity and presynaptic neurotransmitter release. Post-synaptic calcium influx through voltage-gated calcium channels and glutamate-gated receptors activates signaling cascades that turn on transcriptional regulators in the nucleus, which subsequently initiate the transcription of a later wave of genes that are important for synaptic maturation and refinement. However, in the visual system, the identity and function of these waves of gene expression are incompletely understood. The findings in this dissertation elucidate the genes that are induced in the mouse dorsal lateral geniculate nucleus (dLGN) of the thalamus upon exposure to visual stimuli, and elucidate the way in which one candidate gene mediates the appropriate connectivity and refinement of the retinogeniculate synapse—the connection between retinal ganglion cells (RGCs) to thalamocortical relay (TC) neurons.
We hypothesized that genes that are induced by visual experience in post-synaptic TC neurons might be likely candidate regulators of retinogeniculate synaptic refinement. To test this hypothesis, we first performed whole-tissue and single-nucleus RNA sequencing (snRNA-seq) of the dLGN following one week of dark rearing from postnatal day (P)20 to P27, which spans the vision sensitive period of retinogeniculate synapse refinement, and subsequent exposure to light. The results of our snRNA-seq identified hundreds of significantly upregulated genes in excitatory TC neurons after dark rearing and light exposure. We focused our study on a highly induced gene in TC neurons, Tnfrsf12a, which encodes the cell surface pro-inflammatory cytokine receptor TNF receptor superfamily member 12a, referred to as Fn14. Genetic ablation of Fn14 results in structurally smaller and an increased number of functionally weak RGC inputs relative to wild-type mice at P27, suggesting that Fn14 expression is critical for proper functional and anatomical wiring of the retinogeniculate synapse during the vision sensitive period. These findings indicate that visual experience induces the transcription of genes that are critical for normal refinement of the retinogeniculate synapse.
Medical Sciences
Advisors/Committee Members: Bean, Bruce (advisor), Goodrich, Lisa (committee member), Kaplan, Joshua (committee member), Turrigiano, Gina (committee member).
Subjects/Keywords: Synapse; Transcription
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APA (6th Edition):
Tzeng, C. (2019). Regulation of Synapse Refinement by Visual Experience-Dependent Transcription. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029688
Chicago Manual of Style (16th Edition):
Tzeng, Christopher. “Regulation of Synapse Refinement by Visual Experience-Dependent Transcription.” 2019. Doctoral Dissertation, Harvard University. Accessed February 23, 2020.
http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029688.
MLA Handbook (7th Edition):
Tzeng, Christopher. “Regulation of Synapse Refinement by Visual Experience-Dependent Transcription.” 2019. Web. 23 Feb 2020.
Vancouver:
Tzeng C. Regulation of Synapse Refinement by Visual Experience-Dependent Transcription. [Internet] [Doctoral dissertation]. Harvard University; 2019. [cited 2020 Feb 23].
Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029688.
Council of Science Editors:
Tzeng C. Regulation of Synapse Refinement by Visual Experience-Dependent Transcription. [Doctoral Dissertation]. Harvard University; 2019. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029688
University of Hong Kong
10.
Yuan, Yuan.
Transcriptional regulation of mouse secretin receptor in
hypothalamic cells.
Degree: PhD, 2011, University of Hong Kong
URL: Yuan,
Y.
[袁媛].
(2011).
Transcriptional
regulation
of
mouse
secretin
receptor
in
hypothalamic
cells.
(Thesis).
University
of
Hong
Kong,
Pokfulam,
Hong
Kong
SAR.
Retrieved
from
http://dx.doi.org/10.5353/th_b4775293
;
http://dx.doi.org/10.5353/th_b4775293
;
http://hdl.handle.net/10722/174473
► As a neuropeptide, both secretin and secretin receptor are expressed in the central nervous system (CNS). It has been revealed that the activities of…
(more)
▼ As a neuropeptide, both secretin and secretin
receptor are expressed in the central nervous system (CNS). It has
been revealed that the activities of secretin on hypothalamic cells
of rodents are important for osmoregulation and food intake. In the
present study, embryonic mouse hypothalamic cell line N42 was used
to study the promoter activity of mouse secretin receptor (mSR). By
5′ deletion analysis, a promoter element was identified within ?282
to ?443, relative to the ATG codon, and it contains a GC-box (-297
to -286), a ras responsive element (RRE) (-289 to -276) and an
E-box (-416 to -411). Electrophoretic mobility shift assay (EMSA)
and supershift analyses showed that Sp1 interacted with the GC-box,
another zinc finger As a neuropeptide, both secretin and secretin
receptor are expressed in the central nervous system (CNS). It has
been revealed that the activities of secretin on hypothalamic cells
of rodents are important for osmoregulation and food intake. In the
present study, embryonic mouse hypothalamic cell line N42 was used
to study the promoter activity of mouse secretin receptor (mSR). By
5′ deletion analysis, a promoter element was identified within ?282
to ?443, relative to the ATG codon, and it contains a GC-box (-297
to -286), a ras responsive element (RRE) (-289 to -276) and an
E-box (-416 to -411). Electrophoretic mobility shift assay (EMSA)
and supershift analyses showed that Sp1 interacted with the GC-box,
another zinc finger
published_or_final_version
Biological Sciences
Doctoral
Doctor of Philosophy
Advisors/Committee Members: Chow, BKC.
Subjects/Keywords: Genetic transcription - Regulation.; Secretin - Receptors.; Transcription factors.
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Manager
APA (6th Edition):
Yuan, Y. (2011). Transcriptional regulation of mouse secretin receptor in
hypothalamic cells. (Doctoral Dissertation). University of Hong Kong. Retrieved from Yuan, Y. [袁媛]. (2011). Transcriptional regulation of mouse secretin receptor in hypothalamic cells. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4775293 ; http://dx.doi.org/10.5353/th_b4775293 ; http://hdl.handle.net/10722/174473
Chicago Manual of Style (16th Edition):
Yuan, Yuan. “Transcriptional regulation of mouse secretin receptor in
hypothalamic cells.” 2011. Doctoral Dissertation, University of Hong Kong. Accessed February 23, 2020.
Yuan, Y. [袁媛]. (2011). Transcriptional regulation of mouse secretin receptor in hypothalamic cells. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4775293 ; http://dx.doi.org/10.5353/th_b4775293 ; http://hdl.handle.net/10722/174473.
MLA Handbook (7th Edition):
Yuan, Yuan. “Transcriptional regulation of mouse secretin receptor in
hypothalamic cells.” 2011. Web. 23 Feb 2020.
Vancouver:
Yuan Y. Transcriptional regulation of mouse secretin receptor in
hypothalamic cells. [Internet] [Doctoral dissertation]. University of Hong Kong; 2011. [cited 2020 Feb 23].
Available from: Yuan, Y. [袁媛]. (2011). Transcriptional regulation of mouse secretin receptor in hypothalamic cells. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4775293 ; http://dx.doi.org/10.5353/th_b4775293 ; http://hdl.handle.net/10722/174473.
Council of Science Editors:
Yuan Y. Transcriptional regulation of mouse secretin receptor in
hypothalamic cells. [Doctoral Dissertation]. University of Hong Kong; 2011. Available from: Yuan, Y. [袁媛]. (2011). Transcriptional regulation of mouse secretin receptor in hypothalamic cells. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4775293 ; http://dx.doi.org/10.5353/th_b4775293 ; http://hdl.handle.net/10722/174473
University of Hong Kong
11.
Wang, Shimeng.
Characterization of a universal stress protein UspA1171
of Burkholderia caribensis MBA4.
Degree: M. Phil., 2016, University of Hong Kong
URL: http://hdl.handle.net/10722/249195
► Burkholderia caribensis MBA4 is able to utilize haloacetic acids as growth substrates. A key enzyme, dehalogenase Deh4a, that enables bioremediation of halogenated organic compounds, was…
(more)
▼ Burkholderia caribensis MBA4 is able to utilize
haloacetic acids as growth substrates. A key enzyme, dehalogenase
Deh4a, that enables bioremediation of halogenated organic
compounds, was isolated from MBA4. A haloacid operon, which
consists the structural genes for Deh4a and a transporter, Deh4p,
was identified and characterized. So far, the
transcription of this
operon was found to regulate negatively. However, the mechanism has
not been fully understood. Recently, a protein designated as
TetR6620, encoded by gene K788_006620, has been found to bind to
DNA fragment containing 100-bp of upstream non-coding region of the
haloacid operon. Previous study showed that cell extracts prepared
from glycolate-grown MBA4 produced two retardation complexes, A
& B. When gene K788_006620 was disrupted in a mutant, Ins6620,
the formation of the retardation complex A was abolished. Moreover,
when purified recombinant TetR6620 with an N-terminal histidine-tag
was used in similar bandshift assay, at least two retardation
complexes were detected. The mobilities of these complexes are
different from that of complexes A & B identified previously.
When recombinant TetR6620 was supplemented to cell extracts of
glycolate-grown Ins6620, the formation of complex A was restored.
These suggest that while TetR6620 is able to bind to the upstream
non-coding region of the haloacid operon, it probably interacted
with another protein to perform its binding activity. By means of
pull-down experiment, a universal stress protein UspA1171, encode
by gene K788_001171, was envisaged to interact with TetR6620.
In this study, the role of UspA1171 was characterized. A
K788_001171 disruptant was constructed. Plasmid pKNOCK-Cm was used
as a backbone and a derivative containing part of K788_001171 was
used to disrupt gene K788_001171 in MBA4. If UspA1171 is a
repressor for the haloacid operon, then a disruptant will have a
relieved expression of Deh4a in glycolate-grown cells. Quantitative
RT-PCR will be used to determine the expression levels of deh4a.
The results showed that the slow migrating retardation complex A,
identified in wildtype MBA4, was not found in glycolate-grown
Ins6620. The gene K788_001171 has been amplified from the genome of
MBA4 and cloned into an E. coli expression vector pET-14b. The
plasmid was constructed and used to express UspA1171 in E. coli
BL21(DE3). The recombinant histidine-tagged UspA1171 was
over-expressed, purified and used in immobilized-metal affinity
chromatography (IMAC) to pull down proteins that might interact
with it. In addition, UspA1171 was used in BS3 crosslinking
experiments with TetR6620. Western blot analysis was used to verify
their interaction. The IMAC results showed that a 24 kDa protein
was successfully pulled down from glycolate-grown Ins1171 by
UspA1171 conjugated Ni-NTA agarose column. Previous results of
chemical crosslinking showed that TetR6620 can form dimer but there
is no evidence of UspA1171 capable of forming dimer. Nonetheless,
with the presence of UspA1171 and BS3 crosslinker, there…
Advisors/Committee Members: Wong, AOL, Tsang, JSH.
Subjects/Keywords: Genetic transcription - Regulation; Bacterial genetics; Transcription factors
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wang, S. (2016). Characterization of a universal stress protein UspA1171
of Burkholderia caribensis MBA4. (Masters Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/249195
Chicago Manual of Style (16th Edition):
Wang, Shimeng. “Characterization of a universal stress protein UspA1171
of Burkholderia caribensis MBA4.” 2016. Masters Thesis, University of Hong Kong. Accessed February 23, 2020.
http://hdl.handle.net/10722/249195.
MLA Handbook (7th Edition):
Wang, Shimeng. “Characterization of a universal stress protein UspA1171
of Burkholderia caribensis MBA4.” 2016. Web. 23 Feb 2020.
Vancouver:
Wang S. Characterization of a universal stress protein UspA1171
of Burkholderia caribensis MBA4. [Internet] [Masters thesis]. University of Hong Kong; 2016. [cited 2020 Feb 23].
Available from: http://hdl.handle.net/10722/249195.
Council of Science Editors:
Wang S. Characterization of a universal stress protein UspA1171
of Burkholderia caribensis MBA4. [Masters Thesis]. University of Hong Kong; 2016. Available from: http://hdl.handle.net/10722/249195
Portland State University
12.
Eustis, Robyn Lynn.
The Role of <i>Pyrococcus furiosus</i> Transcription Factor E in Transcription Iniitiation.
Degree: MS(M.S.) in Biology, Biology, 2015, Portland State University
URL: https://pdxscholar.library.pdx.edu/open_access_etds/2522
► All sequenced archaeal genomes encode a general transcription factor, TFE, which is highly conserved and homologous to the alpha subunit of the eukaryotic transcription…
(more)
▼ All sequenced archaeal genomes encode a general
transcription factor, TFE, which is highly conserved and homologous to the alpha subunit of the eukaryotic
transcription factor TFIIE. TFE functions to increase promoter opening efficiency during
transcription initiation, although the mechanism for this is unclear. The N-terminus of TFE contains a common DNA binding motif, a winged helix. At the tip of this winged helix is a highly conserved region of aromatic amino acids that is close to DNA during initiation. TFE activation can compensate for mutations in another
transcription factor, TFB2, which is homologous to TFIIB. P.
furiosus encodes two paralogs of the eukaryotic RNA polymerase II
transcription factor TFIIB: TFB1 and TFB2. TFB2 lacks a portion of the highly conserved N-terminus, and functions in
transcription complexes at a lower efficiency than TFB1. It has been demonstrated that the presence of TFE is able to assist in
transcription with TFB2
in vitro bringing its efficiency to almost TFB1 levels. Thus, TFB2 provides a unique opportunity to evaluate the function of the TFE winged helix in
transcription. In this study the aromatic patch of the TFE winged helix was mutated to test its role in activation of TFB1 and TFB2-containing
transcription complexes, because this aromatic patch is required for full TFE activity especially when NTP concentrations are low.
Advisors/Committee Members: Michael Bartlett.
Subjects/Keywords: Archaebacteria; Transcription factors; Genetic transcription; Biology
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APA (6th Edition):
Eustis, R. L. (2015). The Role of <i>Pyrococcus furiosus</i> Transcription Factor E in Transcription Iniitiation. (Masters Thesis). Portland State University. Retrieved from https://pdxscholar.library.pdx.edu/open_access_etds/2522
Chicago Manual of Style (16th Edition):
Eustis, Robyn Lynn. “The Role of <i>Pyrococcus furiosus</i> Transcription Factor E in Transcription Iniitiation.” 2015. Masters Thesis, Portland State University. Accessed February 23, 2020.
https://pdxscholar.library.pdx.edu/open_access_etds/2522.
MLA Handbook (7th Edition):
Eustis, Robyn Lynn. “The Role of <i>Pyrococcus furiosus</i> Transcription Factor E in Transcription Iniitiation.” 2015. Web. 23 Feb 2020.
Vancouver:
Eustis RL. The Role of <i>Pyrococcus furiosus</i> Transcription Factor E in Transcription Iniitiation. [Internet] [Masters thesis]. Portland State University; 2015. [cited 2020 Feb 23].
Available from: https://pdxscholar.library.pdx.edu/open_access_etds/2522.
Council of Science Editors:
Eustis RL. The Role of <i>Pyrococcus furiosus</i> Transcription Factor E in Transcription Iniitiation. [Masters Thesis]. Portland State University; 2015. Available from: https://pdxscholar.library.pdx.edu/open_access_etds/2522
Portland State University
13.
Micorescu, Michael.
The Function of an Alternate TFB from Pyrococus furiosus and the Orientation of the TFB B-reader within Archaeal Transcription Initiation Complexes.
Degree: PhD, Biology, 2010, Portland State University
URL: http://pdxscholar.library.pdx.edu/open_access_etds/278
► The genome of the hyperthermophile archaeon Pyrococcus furiosus encodes two transcription factor B (TFB) paralogs, one of which (TFB1) was previously characterized in transcription…
(more)
▼ The genome of the hyperthermophile archaeon Pyrococcus furiosus encodes two
transcription factor B (TFB) paralogs, one of which (TFB1) was previously characterized in
transcription initiation. The second TFB (TFB2) is unusual in that it lacks recognizable homology to the archaeal TFB/eukaryotic TFIIB B-reader (also called the B-finger) motif. TFB2 functions, though poorly, in promoter-dependent
transcription initiation. Domain swaps between TFB1 and TFB2 showed that the low activity of TFB2 is determined mainly by its N terminus. The low activity of TFB2 in promoter opening and
transcription can be partially relieved by
transcription factor E (TFE). The results indicate that the TFB N-terminal region, containing conserved Zn ribbon and B-finger motifs, is important in promoter opening and that TFE can compensate for defects in the N terminus through enhancement of promoter opening. Archaeal RNA polymerase requires two
transcription factors for initiation: TBP, which binds to TATA boxes, and TFB, which binds TBP and DNA, recruits RNAP and helps initiate
transcription. Archaeal TFBs usually contain a conserved B-reader sequence homologous to the eukaryotic B-reader motif in their N-terminal domains. This region is involved in the assembly of the
transcription complex, promoter melting and in
transcription start site determination but its position and orientation relative to promoter DNA during initiation is not clear. In this study the positioning of the TFB B-reader relative to DNA was determined by cross-linking using TFB variants substituted with photoactivatable unnatural amino acids. The results demonstrate that the B-reader is in close proximity to the
transcription start site on the template but not the non-template strand in
transcription initiation complexes. Furthermore, the position of the B-reader varies between closed and open promoter complexes, and between open promoter and early initiation complexes. Thus the archaeal B-reader sequence is poised to interact with promoter DNA in a dynamic fashion, and is likely playing a role in positioning the template-strand in an open pre-initiation complex.
Advisors/Committee Members: Michael S. Bartlett.
Subjects/Keywords: RNA polymerases; Genetic transcription; Transcription factors
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Record Details
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Micorescu, M. (2010). The Function of an Alternate TFB from Pyrococus furiosus and the Orientation of the TFB B-reader within Archaeal Transcription Initiation Complexes. (Doctoral Dissertation). Portland State University. Retrieved from http://pdxscholar.library.pdx.edu/open_access_etds/278
Chicago Manual of Style (16th Edition):
Micorescu, Michael. “The Function of an Alternate TFB from Pyrococus furiosus and the Orientation of the TFB B-reader within Archaeal Transcription Initiation Complexes.” 2010. Doctoral Dissertation, Portland State University. Accessed February 23, 2020.
http://pdxscholar.library.pdx.edu/open_access_etds/278.
MLA Handbook (7th Edition):
Micorescu, Michael. “The Function of an Alternate TFB from Pyrococus furiosus and the Orientation of the TFB B-reader within Archaeal Transcription Initiation Complexes.” 2010. Web. 23 Feb 2020.
Vancouver:
Micorescu M. The Function of an Alternate TFB from Pyrococus furiosus and the Orientation of the TFB B-reader within Archaeal Transcription Initiation Complexes. [Internet] [Doctoral dissertation]. Portland State University; 2010. [cited 2020 Feb 23].
Available from: http://pdxscholar.library.pdx.edu/open_access_etds/278.
Council of Science Editors:
Micorescu M. The Function of an Alternate TFB from Pyrococus furiosus and the Orientation of the TFB B-reader within Archaeal Transcription Initiation Complexes. [Doctoral Dissertation]. Portland State University; 2010. Available from: http://pdxscholar.library.pdx.edu/open_access_etds/278
Latrobe University
14.
Do, Hai Thanh.
Transcription factor binding sites identification using machine learning techniques.
Degree: PhD, 2011, Latrobe University
URL: http://hdl.handle.net/1959.9/527233
► Thesis (Ph.D.) - La Trobe University, 2011
Submission note: "A thesis submitted in total fulfilment of the requirements for the degree of Doctor of Philosophy…
(more)
Subjects/Keywords: Transcription factors.; Genetic transcription.; Gene expression.
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Do, H. T. (2011). Transcription factor binding sites identification using machine learning techniques. (Doctoral Dissertation). Latrobe University. Retrieved from http://hdl.handle.net/1959.9/527233
Chicago Manual of Style (16th Edition):
Do, Hai Thanh. “Transcription factor binding sites identification using machine learning techniques.” 2011. Doctoral Dissertation, Latrobe University. Accessed February 23, 2020.
http://hdl.handle.net/1959.9/527233.
MLA Handbook (7th Edition):
Do, Hai Thanh. “Transcription factor binding sites identification using machine learning techniques.” 2011. Web. 23 Feb 2020.
Vancouver:
Do HT. Transcription factor binding sites identification using machine learning techniques. [Internet] [Doctoral dissertation]. Latrobe University; 2011. [cited 2020 Feb 23].
Available from: http://hdl.handle.net/1959.9/527233.
Council of Science Editors:
Do HT. Transcription factor binding sites identification using machine learning techniques. [Doctoral Dissertation]. Latrobe University; 2011. Available from: http://hdl.handle.net/1959.9/527233
Portland State University
15.
Sheffield, Kimberly Kay.
Interplay of Transcription Factor E and Spt4/5 During Transcription Initiation in <i>Pyrococcus furiosus</i>.
Degree: MS(M.S.) in Biology, Biology, 2018, Portland State University
URL: https://pdxscholar.library.pdx.edu/open_access_etds/4444
► Transcription, the first step in gene expression, is a highly regulated process which relies on a multi-protein complex to occur. Among these proteins are…
(more)
▼ Transcription, the first step in gene expression, is a highly regulated process which relies on a multi-protein complex to occur. Among these proteins are
transcription factors, including initiation and elongation factors, which play differing roles in early and late stages of
transcription. The mechanisms of transition from
transcription initiation to elongation are not well understood in archaea, nor are the structures of the
transcription factors involved. For
transcription to occur
in vitro,
transcription factors TATA binding protein (TBP) and
Transcription Factor B (TFB) are sufficient to allow RNA polymerase (RNAP) to synthesize RNA from template DNA. Another factor,
Transcription Factor E (TFE), can also join the initiation complex and is likely to be essential in vivo. TFE is known to contribute to initiation by enhancing promoter opening, and while it has been shown to persist in elongation complexes, its role after initiation is unknown. Spt4/5, the archaeal homolog of the only universally conserved RNAP-associated factor, is known to join complexes in elongation steps and enhance processivity of the polymerase. However, if Spt4/5 joins pre-initiated complexes, it has been shown to inhibit
transcription activity. The experiments in this thesis show that TFE and Spt4/5 participate in a crucial interchange at the upstream fork of the
transcription bubble that helps define the timing of Spt4/5 binding. Using unnatural amino acid crosslinking techniques, the points of proximity between specific regions of these two factors and the template DNA have been mapped to identify possible sites of interaction. Competitive crosslinking assays indicate the exact timing of the shift in affinity between TFE and Spt4/5 for their shared binding site on RNAP. These data, combined with
transcription assays, suggest a new role for TFE in preventing premature Spt4/5 binding, corresponding with a unique localized mobility within the winged helix of TFE.
Advisors/Committee Members: Michael Bartlett.
Subjects/Keywords: Archaebacteria; Transcription factors; Genetic transcription; Biology
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APA (6th Edition):
Sheffield, K. K. (2018). Interplay of Transcription Factor E and Spt4/5 During Transcription Initiation in <i>Pyrococcus furiosus</i>. (Masters Thesis). Portland State University. Retrieved from https://pdxscholar.library.pdx.edu/open_access_etds/4444
Chicago Manual of Style (16th Edition):
Sheffield, Kimberly Kay. “Interplay of Transcription Factor E and Spt4/5 During Transcription Initiation in <i>Pyrococcus furiosus</i>.” 2018. Masters Thesis, Portland State University. Accessed February 23, 2020.
https://pdxscholar.library.pdx.edu/open_access_etds/4444.
MLA Handbook (7th Edition):
Sheffield, Kimberly Kay. “Interplay of Transcription Factor E and Spt4/5 During Transcription Initiation in <i>Pyrococcus furiosus</i>.” 2018. Web. 23 Feb 2020.
Vancouver:
Sheffield KK. Interplay of Transcription Factor E and Spt4/5 During Transcription Initiation in <i>Pyrococcus furiosus</i>. [Internet] [Masters thesis]. Portland State University; 2018. [cited 2020 Feb 23].
Available from: https://pdxscholar.library.pdx.edu/open_access_etds/4444.
Council of Science Editors:
Sheffield KK. Interplay of Transcription Factor E and Spt4/5 During Transcription Initiation in <i>Pyrococcus furiosus</i>. [Masters Thesis]. Portland State University; 2018. Available from: https://pdxscholar.library.pdx.edu/open_access_etds/4444
University of Oklahoma
16.
Zhao, Tao.
Split ends (spen), A TRANSCRIPTIONAL REGULATOR, INHIBITS MYOSIN ACTIVITY TO REGULATE NEURONAL REMODELING DURING METAMORPHOSIS.
Degree: PhD, 2011, University of Oklahoma
URL: http://hdl.handle.net/11244/318596
► Animal neurons dynamically change their morphologies in response to steroid hormone signaling to adapt to changing environments. The molecular mechanisms underlying animal neuronal remodeling, however,…
(more)
▼ Animal neurons dynamically change their morphologies in response to steroid hormone signaling to adapt to changing environments. The molecular mechanisms underlying animal neuronal remodeling, however, remain largely unknown. Metamorphosis is an important developmental stage in insects when crawling and feeding larvae transform into reproductive and flying adults. During this period, many insect larval neurons undergo dramatic morphological and functional alterations. These neuronal changes are regulated by a arthropod-specific steroid hormone, 20-hydroxyecdysone (ecdysone). Research on the metamorphic remodeling of insect neurons, has provided insights into the general neuronal remodeling process. During the early stage of metamorphosis, the larval neurons prune their projections and then grow out adult-specific neurites. A group of Drosophila melanogaster (fruit fly) neuroendocrine cells, the crustacean cardioactive peptide (CCAP) neurons, experiences metamorphic remodeling, and I used these neurons to dissect the molecular mechanisms controlling this process. The CCAP neurons mainly produce two neuropeptides, CCAP and bursicon, to control insect molting-related behaviors, ecdysis and wing expansion. Functional disruption of the CCAP neuron remodeling leads to defective wing expansion in adults. In a genetic screen, thousands of genes were mis- or overexpressed in the CCAP neurons. The genes that produced strong wing expansion defects were identified. Fourteen of the identified genes specifically inhibited the outgrowth of adult-specific neurites during metamorphic remodeling. One of these, split ends (spen) was selected to identify the molecular pathways affected by its overexpression. I performed a deficiency modifier screen to identify mutations that modify the outgrowth defects induced by spen. A mutation of Mbs, the gene encoding the Myosin binding subunit, moderately suppressed the outgrowth defects. Since Mbs negatively regulates myosin II activity, the results suggested that spen overexpressin suppressed myosin II activity. Another myosinmodulating signaling pathway, Rac1-PAK, was also tested to confirm the observations. The Rac1-PAK signaling pathway positively regulates myosin II function, and this pathway suppressed the neurite outgrowth defects induced by spen overexpression. Furthermore, down-regulation of spen activity strongly rescued the wing expansion and neurite growth defects resulting from disrupted Rac1-PAK signaling. These results strongly support a model in which spen functions antagonistically with myosin II to regulate neuronal outgrowth during metamorphosis.
Advisors/Committee Members: Hewes, Randall S (advisor).
Subjects/Keywords: Neurons; Genetic transcription – Regulation; Transcription factors
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APA ·
Chicago ·
MLA ·
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to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zhao, T. (2011). Split ends (spen), A TRANSCRIPTIONAL REGULATOR, INHIBITS MYOSIN ACTIVITY TO REGULATE NEURONAL REMODELING DURING METAMORPHOSIS. (Doctoral Dissertation). University of Oklahoma. Retrieved from http://hdl.handle.net/11244/318596
Chicago Manual of Style (16th Edition):
Zhao, Tao. “Split ends (spen), A TRANSCRIPTIONAL REGULATOR, INHIBITS MYOSIN ACTIVITY TO REGULATE NEURONAL REMODELING DURING METAMORPHOSIS.” 2011. Doctoral Dissertation, University of Oklahoma. Accessed February 23, 2020.
http://hdl.handle.net/11244/318596.
MLA Handbook (7th Edition):
Zhao, Tao. “Split ends (spen), A TRANSCRIPTIONAL REGULATOR, INHIBITS MYOSIN ACTIVITY TO REGULATE NEURONAL REMODELING DURING METAMORPHOSIS.” 2011. Web. 23 Feb 2020.
Vancouver:
Zhao T. Split ends (spen), A TRANSCRIPTIONAL REGULATOR, INHIBITS MYOSIN ACTIVITY TO REGULATE NEURONAL REMODELING DURING METAMORPHOSIS. [Internet] [Doctoral dissertation]. University of Oklahoma; 2011. [cited 2020 Feb 23].
Available from: http://hdl.handle.net/11244/318596.
Council of Science Editors:
Zhao T. Split ends (spen), A TRANSCRIPTIONAL REGULATOR, INHIBITS MYOSIN ACTIVITY TO REGULATE NEURONAL REMODELING DURING METAMORPHOSIS. [Doctoral Dissertation]. University of Oklahoma; 2011. Available from: http://hdl.handle.net/11244/318596
University of Central Florida
17.
Zhang, Xiaolei.
Discovery and Optimization of Novel Small-molecular Inhibitors Suppressing Stat3-dependent Tumor Process.
Degree: 2011, University of Central Florida
URL: https://stars.library.ucf.edu/etd/6681
► With the critical role of aberrantly active Signal Transducer and Activator of Transcription (Stat) 3 protein in many human cancers, selective small-molecule inhibitors targeting…
(more)
▼ With the critical role of aberrantly active Signal Transducer and Activator of
Transcription (Stat) 3 protein in many human cancers, selective small-molecule inhibitors targeting the dimerization event which is required for stat3 activation, would be valuable as therapeutic agents. And the inhibitors will be useful chemical probes to clarify the complex biological functions of Stat3. By computational and structural analyses of the interaction between Stat3 and the lead dimerization disruptor, S3I-201, we have designed a diverse set of analogs. One of the most active analogs, S3I-201.1066 is derived to contain a cyclo-hexyl benzyl moiety on the amide nitrogen, which increases the binding to the Stat3 SH2 domain. Evidence is presented from in vitro biochemical and biophysical studies that S3I-201.1066 directly interacts with Stat3 or the SH2 domain, with an affinity (K[subscript D]) of 2.74 [micrometer], and disrupts the binding of Stat3 to the cognate pTyr-peptide, GpYLPQTV-NH2, with an IC₅₀ of 23 [micrometer]. Moreover, S3I-201.1066 selectively blocks the association of Stat3 with the epidermal growth factor receptor (EGFR), and inhibits Stat3 tyrosine phosphorylation and nuclear translocation in EGF-stimulated mouse fibroblasts. In cancer cells that harbor aberrant Stat3 activity, S3I-201.1066 inhibits constitutive Stat3 DNA-binding and transcriptional activities.
By contrast, S3I-201.1066 has no effect on Src activation or the EGFR-mediated activation of the Erk1/2MAPK pathway. S3I-201.1066 selectively suppresses the viability, survival, and malignant transformation of the human breast and pancreatic cancer lines and the v-Src-transformed mouse fibroblasts harboring persistently active Stat3. Treatment with S3I-201.1066 on malignant cells harboring aberrantly active Stat3 down regulated the expression of c-Myc, Bcl-xL, Survivin, matrix metalloproteinase 9, and VEGF, which are known Stat3-regulated genes important in diverse tumor processes. The in vivo administration of S3I-201.1066 induced significant anti-tumor response in mouse models of human breast cancer, which correlates with the inhibition of constitutively active Stat3 and the suppression of known Stat3-regulated genes. Further computer-aided lead optimization derives higher-affinity (K[subscript D], 504 nM), orally bioavailable Stat3 SH2 domain-binding ligand, BP-1-102 as a structural analog of S3I-201.1066. The most significant modification is the pentafluorobenzene sulfonamide component of BP-1-102, which permits accessibility of a third sub-pocket of the Stat3 SH2 domain surface. BP-1-102-mediated inhibition of aberrantly-active Stat3 in human pancreatic cancer, Panc-1, breast cancer, MDA-MB-231, and prostate (DU145) cancer cells and in the mouse transformed fibroblasts harboring aberrantly-active Stat3.
It also disrupts Stat3-NF[kappa]B cross-talk and suppresses the release of granulocyte colony-stimulating factor, soluble intercellular adhesion molecule-1, macrophage-migration-inhibitory factor/glycosylation-inhibiting factor,…
Advisors/Committee Members: Turkson, James.
Subjects/Keywords: Transcription factors; STAT3 Transcription Factor; Medical Sciences
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MLA ·
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APA (6th Edition):
Zhang, X. (2011). Discovery and Optimization of Novel Small-molecular Inhibitors Suppressing Stat3-dependent Tumor Process. (Doctoral Dissertation). University of Central Florida. Retrieved from https://stars.library.ucf.edu/etd/6681
Chicago Manual of Style (16th Edition):
Zhang, Xiaolei. “Discovery and Optimization of Novel Small-molecular Inhibitors Suppressing Stat3-dependent Tumor Process.” 2011. Doctoral Dissertation, University of Central Florida. Accessed February 23, 2020.
https://stars.library.ucf.edu/etd/6681.
MLA Handbook (7th Edition):
Zhang, Xiaolei. “Discovery and Optimization of Novel Small-molecular Inhibitors Suppressing Stat3-dependent Tumor Process.” 2011. Web. 23 Feb 2020.
Vancouver:
Zhang X. Discovery and Optimization of Novel Small-molecular Inhibitors Suppressing Stat3-dependent Tumor Process. [Internet] [Doctoral dissertation]. University of Central Florida; 2011. [cited 2020 Feb 23].
Available from: https://stars.library.ucf.edu/etd/6681.
Council of Science Editors:
Zhang X. Discovery and Optimization of Novel Small-molecular Inhibitors Suppressing Stat3-dependent Tumor Process. [Doctoral Dissertation]. University of Central Florida; 2011. Available from: https://stars.library.ucf.edu/etd/6681
University of Alberta
18.
Clelland, Brett William.
Studies on the control of tRNA transcription by the
replication stress checkpoint.
Degree: PhD, Department of Biochemistry, 2011, University of Alberta
URL: https://era.library.ualberta.ca/files/j6731377h
► RNA polymerase III (RNAPIII) pre-initiation complexes at tRNA genes naturally cause replication fork pausing in the yeast Saccharomyces cerevisiae, and interference with replication is known…
(more)
▼ RNA polymerase III (RNAPIII) pre-initiation complexes
at tRNA genes naturally cause replication fork pausing in the yeast
Saccharomyces cerevisiae, and interference with replication is
known to have deleterious effects on genome stability. It follows
that repression of tRNA gene transcription could be advantageous to
minimize replication perturbation. Consistent with this idea, our
lab has previously reported that the replication stress checkpoint
inhibits tRNA gene transcription. Here, I describe how repression
by checkpoint signalling, induced by treatment with the replication
inhibitor hydroxyurea (HU), is associated with RNAPIII
pre-initiation complex disassembly at tRNA genes. In addition, I
show that active checkpoint signals likely impinge on Maf1, a key
negative regulator of RNAPIII transcription, to signal to tRNA
genes during HU exposure. Next, I report that checkpoint signalling
affects the protein complex assemblage at tRNA genes during normal
proliferation. Inactivation of the replication stress checkpoint,
which is associated with an induction of tRNA gene transcription,
results in greater RNAPIII occupancy at tRNA genes and a decrease
in condensin association, condensin being an important tDNA
localized complex that is vital for maintenance of genome
integrity. Next, I extended these results by monitoring replication
in cells with elevated tRNA gene transcription using cross-linking
of replication proteins as proxy for replication fork movement.
Despite the fact that tRNA gene transcription interferes with
replication, by this method I detected no greater fork pausing at
tRNA genes in strains with elevated transcription. These data are
discussed in the context of current controversy in the literature
about this type of replication perturbation. One possibility is
that in cells unable to repress transcription, replication
interference promotes greater genome instability in a way that does
not include amplified fork pausing. Altogether, the results
presented here are in harmony with the idea that the replication
stress checkpoint functions to disassemble RNAPIII transcriptional
machinery, likely to maintain genome stability. Lastly, I present
preliminary data that identifies potential cell division cycle
links to tRNA transcription. We propose a possible new pathway that
restrains tRNA gene transcription involving Cdc28, the main
cyclin-dependent kinase in yeast.
Subjects/Keywords: transcription; tRNA; replication
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APA ·
Chicago ·
MLA ·
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CSE |
Export
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Manager
APA (6th Edition):
Clelland, B. W. (2011). Studies on the control of tRNA transcription by the
replication stress checkpoint. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/j6731377h
Chicago Manual of Style (16th Edition):
Clelland, Brett William. “Studies on the control of tRNA transcription by the
replication stress checkpoint.” 2011. Doctoral Dissertation, University of Alberta. Accessed February 23, 2020.
https://era.library.ualberta.ca/files/j6731377h.
MLA Handbook (7th Edition):
Clelland, Brett William. “Studies on the control of tRNA transcription by the
replication stress checkpoint.” 2011. Web. 23 Feb 2020.
Vancouver:
Clelland BW. Studies on the control of tRNA transcription by the
replication stress checkpoint. [Internet] [Doctoral dissertation]. University of Alberta; 2011. [cited 2020 Feb 23].
Available from: https://era.library.ualberta.ca/files/j6731377h.
Council of Science Editors:
Clelland BW. Studies on the control of tRNA transcription by the
replication stress checkpoint. [Doctoral Dissertation]. University of Alberta; 2011. Available from: https://era.library.ualberta.ca/files/j6731377h
University of Hong Kong
19.
成云; Cheng, Yun.
β-TrCP-mediated ubiquitination and degradation of
liver-enriched transcription factor CREB-H.
Degree: PhD, 2016, University of Hong Kong
URL: Cheng,
Y.
[成云].
(2016).
β-TrCP-mediated
ubiquitination
and
degradation
of
liver-enriched
transcription
factor
CREB-H.
(Thesis).
University
of
Hong
Kong,
Pokfulam,
Hong
Kong
SAR.
Retrieved
from
http://dx.doi.org/10.5353/th_b5816255.
;
http://dx.doi.org/10.5353/th_b5816255
;
http://hdl.handle.net/10722/237862
► CREB-H is an endoplasmic reticulum-tethered bZIP transcription factor, which critically regulates lipid homeostasis and gluconeogenesis in the liver. CREB-H is proteolytically activated by regulated intramembrane…
(more)
▼ CREB-H is an endoplasmic reticulum-tethered bZIP
transcription factor, which critically regulates lipid homeostasis
and gluconeogenesis in the liver. CREB-H is proteolytically
activated by regulated intramembrane proteolysis to generate a
C-terminally truncated form known as CREB-H-ΔTC, which translocates
to the nucleus to activate the expression of target genes. We have
previously characterized the roles and regulation of CREB-H in
hepatic physiology and pathology. As the physiologically active
form of CREB-H, CREB-H-ΔTC is a fast turnover protein. However, the
mechanism governing CREB-H-ΔTC destruction was not well
understood.
In this study, I report on β-TrCP-dependent
ubiquitination and proteasomal degradation of CREB-H-ΔTC. β-TrCP is
the substrate recognition subunit of the E3 ubiquitin ligase
SCF^(β-TrCP), which catalyzes the ubiquitination of various
transcription factors and cell cycle regulatory proteins. By
modulating the steady-state level and activity of these key
factors, β-TrCP plays an important role in cell cycle control,
oncogenesis and metabolic regulation. In my study, I first verified
that the degradation of CREB-H-ΔTC was mediated by lysine 48-linked
polyubiquitination. This degradation was effectively inhibited by a
proteasome inhibitor. In search of the E3 ubiquitin ligase
catalyzing CREB-H-ΔTC ubiquitination, bioinformatic analysis was
carried out and β-TrCP was singled out as a potential E3. In light
of the importance of β-TrCP in CREB-H-ΔTC degradation, experimental
validation was performed. CREB-H-ΔTC physically interacted with
β-TrCP. Forced expression of β-TrCP increased the
polyubiquitination and decreased the stability of CREB-H-ΔTC,
whereas knockdown of β-TrCP had the opposite effect. These results
indicated that CREB-H-ΔTC undergoes β-TrCP-dependent lysine
48-linked polyubiquitination and degradation.
I went on to
characterize the molecular details of β-TrCP-mediated
ubiquitination and degradation of CREB-H-ΔTC. An evolutionarily
conserved sequence, SDSGIS, which functions as the β-TrCP-binding
motif, was identified in CREB-H. CREB-H-ΔTC lacking this motif was
stabilized and resistant to β-TrCP-induced polyubiquitination. This
motif was a phosphodegron and phosphorylation at its serine
residues was required for β-TrCP recognition.
Furthermore, two
additional phosphorylation sites close to the phosphodegron were
identified. Interestingly, mutational analysis suggested that
dephosphorylation of the two sites increased the transcriptional
activity of CREB-H-ΔTC. Based on these results, I propose a new
model for the regulation of CREB-H-ΔTC ubiquitination and
degradation through both inhibitory and activating
phosphorylation.
Taken together, my work not only provided
experimental evidence for β-TrCP-mediated ubiquitination and
degradation of the active form of CREB-H transcription factor, but
also revealed a new intracellular signaling pathway by which its
ubiquitination and degradation are regulated. My findings have
implications in the development of new agents that either…
Subjects/Keywords: Transcription factors; Ubiquitin
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
成云; Cheng, Y. (2016). β-TrCP-mediated ubiquitination and degradation of
liver-enriched transcription factor CREB-H. (Doctoral Dissertation). University of Hong Kong. Retrieved from Cheng, Y. [成云]. (2016). β-TrCP-mediated ubiquitination and degradation of liver-enriched transcription factor CREB-H. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5816255. ; http://dx.doi.org/10.5353/th_b5816255 ; http://hdl.handle.net/10722/237862
Chicago Manual of Style (16th Edition):
成云; Cheng, Yun. “β-TrCP-mediated ubiquitination and degradation of
liver-enriched transcription factor CREB-H.” 2016. Doctoral Dissertation, University of Hong Kong. Accessed February 23, 2020.
Cheng, Y. [成云]. (2016). β-TrCP-mediated ubiquitination and degradation of liver-enriched transcription factor CREB-H. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5816255. ; http://dx.doi.org/10.5353/th_b5816255 ; http://hdl.handle.net/10722/237862.
MLA Handbook (7th Edition):
成云; Cheng, Yun. “β-TrCP-mediated ubiquitination and degradation of
liver-enriched transcription factor CREB-H.” 2016. Web. 23 Feb 2020.
Vancouver:
成云; Cheng Y. β-TrCP-mediated ubiquitination and degradation of
liver-enriched transcription factor CREB-H. [Internet] [Doctoral dissertation]. University of Hong Kong; 2016. [cited 2020 Feb 23].
Available from: Cheng, Y. [成云]. (2016). β-TrCP-mediated ubiquitination and degradation of liver-enriched transcription factor CREB-H. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5816255. ; http://dx.doi.org/10.5353/th_b5816255 ; http://hdl.handle.net/10722/237862.
Council of Science Editors:
成云; Cheng Y. β-TrCP-mediated ubiquitination and degradation of
liver-enriched transcription factor CREB-H. [Doctoral Dissertation]. University of Hong Kong; 2016. Available from: Cheng, Y. [成云]. (2016). β-TrCP-mediated ubiquitination and degradation of liver-enriched transcription factor CREB-H. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5816255. ; http://dx.doi.org/10.5353/th_b5816255 ; http://hdl.handle.net/10722/237862
Penn State University
20.
Wung, Ju-Chieh.
CHARACTERIZATION AND ANALYSIS OF DROSOPHILA PCF11.
Degree: MS, Biochemistry, Microbiology, and Molecular
Biology, 2010, Penn State University
URL: https://etda.libraries.psu.edu/catalog/10768
► Transcription cycle can be divided into three stages: initiation, elongation and termination. The process of transcription termination decreases the elongation rate of RNA polymerase II…
(more)
▼ Transcription cycle can be divided into three stages:
initiation, elongation and termination. The process of
transcription termination decreases the elongation rate of RNA
polymerase II (Pol II) and ultimately disrupts the association of
Pol II with DNA. Termination is essential for recycling Pol II and
for preventing Pol II from interfering with downstream gene
transcription. Pcf11 (protein 1 of CF I) was first identified as a
functional component of yeast cleavage and polyadenylation factor
I. Pcf11 is involved in transcription termination. The Pcf11 mRNA
in FlyBase was annotated by piecing together several cDNA clones,
but only one of the cDNA clones contained a complete open reading
frame. In addition, I observed that Pcf11 RNAi decreased the level
of a protein around 200 kDa, which was different from Dr. Zhang’s
observation. To obtain an assessment of Pcf11 that would be
independent of our Pcf11 antibody, I analyzed Pcf11 mRNA. I
characterized two groups of Pcf11 transcripts, which encode two
forms of Pcf11. One is 63 kDa, the other is 201 kDa Pcf11. Both
large and small forms of Pcf11 have identical protein sequences for
the first 515 amino acid residues, but have different sequences for
the rest of the C-terminus. The N-terminal regions of both proteins
encode the same domain that has been shown to associate with the
carboxyl terminal domain (CTD) of Pol II. Thus, both forms of the
protein could potentially be involved in regulating Pol II. Reverse
transcription PCR (RT-PCR) suggests that the short Pcf11 transcript
is expressed at a significantly higher level in embryos than in
cell lines or larval tissues, and that the long Pcf11 transcript is
expressed at similar levels among various tissues. RT-PCR also
shows that the expression level of the two transcripts is
unaffected by various stresses. A native gel system and an in vitro
dismantling assay were used to analyze the interaction between the
CID (CTD-interacting domain) of Pcf11 and CTD of Rpb1, the largest
subunit of Pol II. The native gel analysis shows that the CID
interacts with the elongation complex mainly via CTD, and that the
CID has a weak interaction with CTD-less Pol II. In contrast to
work previously done in our laboratory, I was unable to detect any
activity associated with Pcf11 that dismantles the elongation
complex. I did find that the CID inhibited elongation by
CTD-containing but not CTD-less Pol II at high nucleotide
concentrations but inhibited both forms of Pol II at low nucleotide
concentrations. I propose that the interaction with the CTD might
contribute to the association of Pcf11 with the Pol II but
interactions with the body of the Pol II are capable of regulating
Pol II transcription.
Subjects/Keywords: transcription termination; Pcf11
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wung, J. (2010). CHARACTERIZATION AND ANALYSIS OF DROSOPHILA PCF11. (Masters Thesis). Penn State University. Retrieved from https://etda.libraries.psu.edu/catalog/10768
Chicago Manual of Style (16th Edition):
Wung, Ju-Chieh. “CHARACTERIZATION AND ANALYSIS OF DROSOPHILA PCF11.” 2010. Masters Thesis, Penn State University. Accessed February 23, 2020.
https://etda.libraries.psu.edu/catalog/10768.
MLA Handbook (7th Edition):
Wung, Ju-Chieh. “CHARACTERIZATION AND ANALYSIS OF DROSOPHILA PCF11.” 2010. Web. 23 Feb 2020.
Vancouver:
Wung J. CHARACTERIZATION AND ANALYSIS OF DROSOPHILA PCF11. [Internet] [Masters thesis]. Penn State University; 2010. [cited 2020 Feb 23].
Available from: https://etda.libraries.psu.edu/catalog/10768.
Council of Science Editors:
Wung J. CHARACTERIZATION AND ANALYSIS OF DROSOPHILA PCF11. [Masters Thesis]. Penn State University; 2010. Available from: https://etda.libraries.psu.edu/catalog/10768
Oregon State University
21.
Smith, Eric Jonathan.
Age-related loss of Nrf2, a novel mechanism for the potential attenuation of xenobiotic detoxification capacity.
Degree: PhD, Biochemistry and Biophysics, 2014, Oregon State University
URL: http://hdl.handle.net/1957/50007
► Nuclear Factor, Erythroid Derived 2, Like 2 (NFE2L2 or Nrf2) is the primary transcription factor in cellular defense against oxidative and xenobiotic stresses in higher…
(more)
▼ Nuclear Factor, Erythroid Derived 2, Like 2 (NFE2L2 or Nrf2) is the primary
transcription factor in cellular defense against oxidative and xenobiotic stresses in higher eukaryotes. This basic leucine zipper
transcription factor regulates over 200 antioxidant, detoxification, and lipid metabolizing genes by binding to the Antioxidant Response Element (ARE; a cis-acting element) as a
transcription enhancer. Our group, and others, have identified that the nuclear steady state levels of this highly inducible
transcription factor declines with age which coincides with decreased expression of many ARE regulated genes. To elucidate the mechanism(s) involved in lowered Nrf2 levels we used hepatocytes isolated from young and old rats as a relevant cellular model that maintains the aging phenotype with respect to Nrf2 levels. Our results show that steady state Nrf2 levels decline by ~40% with age (N=4, p<0.05), which led us to investigate the multifaceted regulation of Nrf2 homeostasis. Specifically, analysis of Nrf2 mRNA levels, and the rate of Nrf2 protein turnover and translation were investigated. Surprisingly, Keap1-mediated degradation of Nrf2, its primary negative regulator, did not account for the age-related Nrf2 decline, nor did mRNA levels change with age. Rather, Nrf2 protein synthesis declines 5.3-fold with age (N=3, p<0.05). Furthermore, we identify that rno-miR-146a, a key inflammation regulating miRNA, both inhibits Nrf2 translation and increases significantly with age. Taken together, our data suggest that the age-related loss of Nrf2 stems from the loss of its translation and may be mediated through miR regulation.
Our lab previously demonstrated in rats, that the age-related loss of Nrf2 consequentially attenuates synthesis and steady state levels of liver glutathione (GSH) synthesis and manifests as a diminished level of GSH. This antioxidant is the most abundant non-protein thiol in most cells and is pivotal for the detoxification of many xenobiotics. The rate-limiting enzyme in GSH synthesis, γ-glutamyl-cysteine ligase (Gcl), is composed of a catalytic (Gclc), and a modulatory (Gclm) subunit. In mice and humans, it is established that Nrf2, through the ARE, regulates Gclc expression. However, this had not been established in rats. From a bioinformatics analysis of the 5’ upstream sequence of the rat Gclc gene, we identified 3 putative AREs (ARE1, ARE3, and ARE4), and one cis-element containing the core but not the flanking nucleotides of the ARE (ARE2). Luciferase reporter plasmids containing each individual ARE were transfected into H4IIE rat hepatoma cells to test for ARE activity. Only one, designated “ARE4”, produced appreciable luciferase activity and was dependent on Nrf2 expression, suggesting that this ARE is a “true” enhancer element. Chromatin immunoprecipitation (ChIP) and qPCR identified that Nrf2 binds ARE4 but not ARE1-3. Further ChIP analysis identified that known partner
transcription factors of Nrf2 (small maf, c-Jun and c-Fos) were also bound to ARE4. Taken together, our data…
Advisors/Committee Members: Hagen, Tory M. (advisor), Ho, Emily (committee member).
Subjects/Keywords: Nrf2; Transcription factors
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APA (6th Edition):
Smith, E. J. (2014). Age-related loss of Nrf2, a novel mechanism for the potential attenuation of xenobiotic detoxification capacity. (Doctoral Dissertation). Oregon State University. Retrieved from http://hdl.handle.net/1957/50007
Chicago Manual of Style (16th Edition):
Smith, Eric Jonathan. “Age-related loss of Nrf2, a novel mechanism for the potential attenuation of xenobiotic detoxification capacity.” 2014. Doctoral Dissertation, Oregon State University. Accessed February 23, 2020.
http://hdl.handle.net/1957/50007.
MLA Handbook (7th Edition):
Smith, Eric Jonathan. “Age-related loss of Nrf2, a novel mechanism for the potential attenuation of xenobiotic detoxification capacity.” 2014. Web. 23 Feb 2020.
Vancouver:
Smith EJ. Age-related loss of Nrf2, a novel mechanism for the potential attenuation of xenobiotic detoxification capacity. [Internet] [Doctoral dissertation]. Oregon State University; 2014. [cited 2020 Feb 23].
Available from: http://hdl.handle.net/1957/50007.
Council of Science Editors:
Smith EJ. Age-related loss of Nrf2, a novel mechanism for the potential attenuation of xenobiotic detoxification capacity. [Doctoral Dissertation]. Oregon State University; 2014. Available from: http://hdl.handle.net/1957/50007
Cornell University
22.
Murphy, Kristin.
Understanding The Molecular Mechanisms Of Transcriptional Repression Mediated By Krab Zinc Finger Proteins And Trim28
.
Degree: 2013, Cornell University
URL: http://hdl.handle.net/1813/34035
► KRAB domain Zinc Finger proteins make up the largest family of transcription factors in mammals. Previous studies on a handful of KRAB Zinc Finger proteins…
(more)
▼ KRAB domain Zinc Finger proteins make up the largest family of
transcription factors in mammals. Previous studies on a handful of KRAB Zinc Finger proteins have demonstrated that KRAB domains possess the ability to repress
transcription, and that this activity is mediated by an interaction with TRIM28. Depleting TRIM28 in mice zygotes results in pre gastrula stage embryonic lethality; however, little is known about how TRIM28 functions with individual KRAB domain proteins to control development. chatwo, an ENU-induced mutation, creates a hypomorphic allele of Trim28. Interestingly, the phenotype of chatwo mutants closely resembles the phenotype of KRAB Zinc Finger protein Zfp568 mutants. My results demonstrate at the molecular level that TRIM28 physically interacts with ZFP568, and is required for ZFP568 to mediate transcriptional repression. I characterized molecularly the Trim28chatwo allele and found that the chatwo mutation impairs the repressive activity of TRIM28, and affects the stability of TRIM28-ZFP568 protein complexes. My results also provide evidence that ZFP568 repressive activity is more severely affected than other KRAB Zinc Finger proteins by TRIM28 depletion, supporting a model in which KRAB Zinc Finger proteins differentially require TRIM28. By studying mutations in KRAB Zinc Finger protein ZFP568, I found that some KRAB motif amino acid residues are more critical than others to mediate transcriptional repression. My results also revealed that TRIM28 binding is not sufficient for KRAB domain repressive activity. By analyzing the repressive activity and ability to bind TRIM28 of a wide collection of KRAB domain proteins, I showed that repressive activities of KRAB domain proteins vary broadly amongst different family members, and importantly, the repressive activities of KRAB Zinc Finger proteins do not correlate with their ability to interact with TRIM28. Overall, this study provides novel contributions to the current understanding of the transcriptional roles of KRAB Zinc Finger proteins.
Advisors/Committee Members: Schimenti, John C. (committeeMember), Wolfner, Mariana Federica (committeeMember).
Subjects/Keywords: embryogenesis;
repression;
transcription
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APA (6th Edition):
Murphy, K. (2013). Understanding The Molecular Mechanisms Of Transcriptional Repression Mediated By Krab Zinc Finger Proteins And Trim28
. (Thesis). Cornell University. Retrieved from http://hdl.handle.net/1813/34035
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Murphy, Kristin. “Understanding The Molecular Mechanisms Of Transcriptional Repression Mediated By Krab Zinc Finger Proteins And Trim28
.” 2013. Thesis, Cornell University. Accessed February 23, 2020.
http://hdl.handle.net/1813/34035.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Murphy, Kristin. “Understanding The Molecular Mechanisms Of Transcriptional Repression Mediated By Krab Zinc Finger Proteins And Trim28
.” 2013. Web. 23 Feb 2020.
Vancouver:
Murphy K. Understanding The Molecular Mechanisms Of Transcriptional Repression Mediated By Krab Zinc Finger Proteins And Trim28
. [Internet] [Thesis]. Cornell University; 2013. [cited 2020 Feb 23].
Available from: http://hdl.handle.net/1813/34035.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Murphy K. Understanding The Molecular Mechanisms Of Transcriptional Repression Mediated By Krab Zinc Finger Proteins And Trim28
. [Thesis]. Cornell University; 2013. Available from: http://hdl.handle.net/1813/34035
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Cornell University
23.
Bird, Jeremy.
Characterization Of Novel Dna Elements Necessary For Sigma-Dependent Promoter Proximal Transcriptional Pausing
.
Degree: 2013, Cornell University
URL: http://hdl.handle.net/1813/34019
► Transcription is not necessarily uniform in rate, but instead consists of multiple periods of continuous elongation by RNA polymerase (RNAP) interrupted by occasional pausing events.…
(more)
▼ Transcription is not necessarily uniform in rate, but instead consists of multiple periods of continuous elongation by RNA polymerase (RNAP) interrupted by occasional pausing events. These pauses have several determined origins, including the interaction of protein co-factors, the influence of transcribed RNA secondary structure, and a direct effect of the sequence composition of the DNA being transcribed. Promoter proximal pauses, in which RNAP pauses tens of nucleotides downstream of the
transcription start site, have been observed in systems ranging from bacteria to more complex eukaryotes such as D. melanogaster and humans, and play important regulatory roles in organisms of all levels. In E. coli, [sigma]70-dependent promoter proximal pauses are of particular interest because lambdoid phage late gene promoters require these pauses for the loading of the anti-terminator Q protein, which is necessary for
transcription of the phage late genes during lytic growth. The primary interaction that induces [sigma]70-dependent pauses is between the non-template strand of the -10-like sequence and [sigma]70 region 2. However, recent evidence identifies other important sequences including several nucleotides around the pause site itself that are required for pausing (Perdue and Roberts 2010). Mutational studies of lambdoid phage 82 promoter pR' show that a 3-bp GC-rich sequence primarily promotes pausing through the template DNA strand, but also acts through a non-template DNA strand interaction with [sigma]70. I show that this template strand sequence determines where the pause occurs. It is likely that in [sigma]-dependent promoterproximal pausing, the [sigma]70/DNA interaction anchors the elongation complex upstream of the pause site, requiring it to "scrunch" (by analogy to scrunching during initial
transcription (Kapanidis et al. 2006)) and to create an enlarged DNA bubble as the active center reaches the pause site. "Scrunched" complexes are energetically strained, but stable at the pause site; my data suggest that the G/C-rich template sequence is a critical element in stabilizing the paused, scrunched structure. Mutational studies of the A/T-rich region demonstrate that the terminal nucleotide of the pause site plays an important role in pause formation, and that the base composition of the A/T-rich sequence determines the likelihood that a
transcription complex escapes the pause. My data also suggest that a [sigma]70-dependent paused
transcription complex enters the paused state through a pretranslocated state of the enzyme. Through these studies, I have expanded the current understanding of the protein/nucleotide and nucleotide/nucleotide interactions that constitute the [sigma]70dependent promoter proximal paused complex.
Advisors/Committee Members: Lis, John T (committeeMember), Alani, Eric E (committeeMember).
Subjects/Keywords: Transcription;
Pausing;
Phage
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bird, J. (2013). Characterization Of Novel Dna Elements Necessary For Sigma-Dependent Promoter Proximal Transcriptional Pausing
. (Thesis). Cornell University. Retrieved from http://hdl.handle.net/1813/34019
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Bird, Jeremy. “Characterization Of Novel Dna Elements Necessary For Sigma-Dependent Promoter Proximal Transcriptional Pausing
.” 2013. Thesis, Cornell University. Accessed February 23, 2020.
http://hdl.handle.net/1813/34019.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Bird, Jeremy. “Characterization Of Novel Dna Elements Necessary For Sigma-Dependent Promoter Proximal Transcriptional Pausing
.” 2013. Web. 23 Feb 2020.
Vancouver:
Bird J. Characterization Of Novel Dna Elements Necessary For Sigma-Dependent Promoter Proximal Transcriptional Pausing
. [Internet] [Thesis]. Cornell University; 2013. [cited 2020 Feb 23].
Available from: http://hdl.handle.net/1813/34019.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Bird J. Characterization Of Novel Dna Elements Necessary For Sigma-Dependent Promoter Proximal Transcriptional Pausing
. [Thesis]. Cornell University; 2013. Available from: http://hdl.handle.net/1813/34019
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Colorado
24.
Ebmeier, Christopher Carl.
Targeted Proteomics and Molecular Mechanisms of Gene Activation.
Degree: PhD, Chemistry & Biochemistry, 2011, University of Colorado
URL: https://scholar.colorado.edu/chem_gradetds/51
► Mass spectrometry-based proteomics is a powerful tool when combined with hypothesis driven protein purification. Regulation of protein-protein interactions is a major molecular mechanism for…
(more)
▼ Mass spectrometry-based proteomics is a powerful tool when combined with hypothesis driven protein purification. Regulation of protein-protein interactions is a major molecular mechanism for gene activation. Protein purification, functional assays, and antibody-based western blots have traditionally been used to elucidate many of the most critical and perhaps universal protein-protein interactions required for gene expression, such as the assembly of the general
transcription machinery. The Mediator complex is an essential part of the general
transcription machinery that integrates signals from DNA-binding transcriptional activators through protein-protein interactions to regulate RNA Pol II activity. Gene activation is ultimately determined by incoming stimuli and subsequent inter-cellular signaling. How these signals are integrated in a spatial and temporal fashion for the regulation of distinct genes by activator-Mediator interactions is unclear. One proposed molecular mechanism of gene activation by the Mediator complex is through a structural shift in the complex. Mediator structural shifts may trigger new protein-protein interactions required for
transcription of select genes in response to a specific stimulus. To test this, Mediator complexes were purified with and without transcriptional activators. The activation domains of the transcriptional activators SREBP-1a and VP16, which generate distinct structures upon binding Mediator, were used to affinity purify activator-bound Mediator complexes. For comparison, antibodies for the Mediator subunits MED1 and CDK8 were used to affinity purify activator-free Mediator complexes. A mass spectrometry-based proteomics platform was established to characterize the protein compositions of each Mediator complex purification. The results showed additional cofactors in the activator-bound Mediator complexes, many of which had known function related to gene expression. Selected cofactors were validated for binding Mediator with an orthogonal purification that combined the activator and antibody purifications and western blotting. Together the proteomics data predicted and the western blotting confirmed new protein-protein interactions relevant for regulation of gene expression that were activator-specific. Collectively, these targeted proteomics approaches have generated many new hypotheses and have fundamentally altered our understanding of how gene expression is regulated.
Advisors/Committee Members: Dylan J. Taatjes, William Old, Natalie Ahn.
Subjects/Keywords: proteomics; transcription; Biochemistry
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ebmeier, C. C. (2011). Targeted Proteomics and Molecular Mechanisms of Gene Activation. (Doctoral Dissertation). University of Colorado. Retrieved from https://scholar.colorado.edu/chem_gradetds/51
Chicago Manual of Style (16th Edition):
Ebmeier, Christopher Carl. “Targeted Proteomics and Molecular Mechanisms of Gene Activation.” 2011. Doctoral Dissertation, University of Colorado. Accessed February 23, 2020.
https://scholar.colorado.edu/chem_gradetds/51.
MLA Handbook (7th Edition):
Ebmeier, Christopher Carl. “Targeted Proteomics and Molecular Mechanisms of Gene Activation.” 2011. Web. 23 Feb 2020.
Vancouver:
Ebmeier CC. Targeted Proteomics and Molecular Mechanisms of Gene Activation. [Internet] [Doctoral dissertation]. University of Colorado; 2011. [cited 2020 Feb 23].
Available from: https://scholar.colorado.edu/chem_gradetds/51.
Council of Science Editors:
Ebmeier CC. Targeted Proteomics and Molecular Mechanisms of Gene Activation. [Doctoral Dissertation]. University of Colorado; 2011. Available from: https://scholar.colorado.edu/chem_gradetds/51
University of Ottawa
25.
Hryniuk, Alexa Kathryn.
The Role of Cdx Transcription Factors in the Adult Intestine
.
Degree: 2015, University of Ottawa
URL: http://hdl.handle.net/10393/32332
► The homeodomain transcription factor family of Cdx genes, Cdx1, Cdx2 and Cdx4, are known to play essential roles in many developmental processes including neural tube…
(more)
▼ The homeodomain transcription factor family of Cdx genes, Cdx1, Cdx2 and Cdx4, are known to play essential roles in many developmental processes including neural tube closure, axial elongation, hematopoiesis and gastrointestinal patterning. In the adult, Cdx1 and Cdx2 are both expressed strictly in the adult intestinal epithelium, but their functions and mechanisms of action at this stage are poorly understood. Cdx transcription factors have also been reported to be lost in intestinal cancers. To circumvent early lethality, a conditional loss of function strategy was used to inactivate Cdx2 in the adult intestinal epithelium. These conditional mutants were crossed to Cdx1-/- mice to examine potential functional compensation between these family members as well as into APC(min/+) mice to study their role in tumorigenesis. Using these models, I have found that Cdx2 regulates adult intestinal homeostasis and differentiation in the small intestinal epithelium, while both Cdx1 and Cdx2 contribute to colon homeostasis. Furthermore, Cdx transcription factors are tumor suppressors in the development of Wnt-induced colorectal cancer, and impact several pathways including TGF-β and Eph-ephrin signaling. Finally, Cdx2 regulates Eph-ephrin signaling through direct activation of the Notch pathway. Altogether, this study underscores critical roles and mechanisms of action for Cdx members in the adult intestine and in intestinal tumorigenesis.
Subjects/Keywords: Transcription factors;
Intestine
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APA ·
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MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hryniuk, A. K. (2015). The Role of Cdx Transcription Factors in the Adult Intestine
. (Thesis). University of Ottawa. Retrieved from http://hdl.handle.net/10393/32332
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Hryniuk, Alexa Kathryn. “The Role of Cdx Transcription Factors in the Adult Intestine
.” 2015. Thesis, University of Ottawa. Accessed February 23, 2020.
http://hdl.handle.net/10393/32332.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Hryniuk, Alexa Kathryn. “The Role of Cdx Transcription Factors in the Adult Intestine
.” 2015. Web. 23 Feb 2020.
Vancouver:
Hryniuk AK. The Role of Cdx Transcription Factors in the Adult Intestine
. [Internet] [Thesis]. University of Ottawa; 2015. [cited 2020 Feb 23].
Available from: http://hdl.handle.net/10393/32332.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Hryniuk AK. The Role of Cdx Transcription Factors in the Adult Intestine
. [Thesis]. University of Ottawa; 2015. Available from: http://hdl.handle.net/10393/32332
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Melbourne
26.
Daniel, Paul Marcel.
Identification of CREB as a transcriptional regulator of glioblastoma biology.
Degree: 2015, University of Melbourne
URL: http://hdl.handle.net/11343/58851
► Glioblastoma (GBM) is both the most common and malignant type of brain tumour with a median survival of 7.4 months from the date of diagnosis;…
(more)
▼ Glioblastoma (GBM) is both the most common and malignant type of brain tumour with a median survival of 7.4 months from the date of diagnosis; even following current treatment regimens of resection, radiation and chemotherapy, highlighting the need for a greater understanding of the molecular mechanisms driving tumour biology. The Cyclic-AMP Response Element Binding (CREB) protein is a kinase-inducible transcription factor which sits at a hub of pro-oncogenic signalling pathways. CREB is a critical regulator of normal brain development where it regulates proliferation, differentiation and survival. The phosphorylated form of CREB (pCREB) is overexpressed in several types of cancer where it regulates various aspects of tumour biology but little is known about the role of CREB in GBM. As such, this thesis hypothesises that pCREB is an oncogene in GBM where it is activated by multiple cancer signalling pathways and is essential for the maintenance of tumour biology.
To investigate the pathways responsible for CREB activation in GBM and the potential of pCREB to serve as a prognostic biomarker, a combination of immunohistochemistry (IHC) and bioinformatics analysis were undertaken. pCREB was co-expressed in cells along with either pMAPK or pAKT in GBM specimens, implicating the PI3K/AKT and MEK/MAPK pathways in differentially activating CREB. Signalling through a MAPK-CREB axis was associated with cell proliferation whilst an AKT-CREB signalling axis was implicated in invasion. pCREB was not prognostic for survival in GBM however was associated with poor prognosis when analysed in the context of MEK/MAPK signalling.
Investigation of the role of CREB in vitro confirmed the role of CREB in regulating proliferation. Knockdown of CREB resulted in slower cell cycle progression and this occurred through the transcriptional regulation of the cell cycle factor Cyclin D1. In addition, CREB was selectively regulated the activity of the PI3K/AKT pathway via a feedback mechanism which in turn regulated the expression of cell cycle factors Cyclin B1 and PCNA.
In contrast to the PI3K/AKT and MEK/MAPK pathways, the cAMP/PKA pathway was not associated with CREB activation in GBM. Exogenous activation of the cAMP/PKA pathway resulted in BIM dependant apoptosis in selective GBM cell lines. CREB played a pro-survival role in this context where it inhibited BIM expression and apoptosis.
To investigate the link between the PI3K/AKT pathway and CREB, hyperactivation of the PI3K/AKT pathway was induced in neural stem cells via an activating mutation of PIK3CA and loss of PTEN, leading to glioma initiation in vivo. Cells with these mutations expressed high levels of pAKT as well as CREB target genes Cyclin D1 and Cyclin B1 independently of exogenous growth factors. pCREB was expressed throughout PIK3CA/PTEN tumours and knockout of CREB in PIK3CA/PTEN tumours resulted in prolonged survival, demonstrating the key role of CREB in PI3K/AKT mediated tumour biology.
Collectively this study establishes CREB as a pro-oncogenic factor in…
Subjects/Keywords: glioblastoma; CREB; transcription
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APA ·
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MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Daniel, P. M. (2015). Identification of CREB as a transcriptional regulator of glioblastoma biology. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/58851
Chicago Manual of Style (16th Edition):
Daniel, Paul Marcel. “Identification of CREB as a transcriptional regulator of glioblastoma biology.” 2015. Doctoral Dissertation, University of Melbourne. Accessed February 23, 2020.
http://hdl.handle.net/11343/58851.
MLA Handbook (7th Edition):
Daniel, Paul Marcel. “Identification of CREB as a transcriptional regulator of glioblastoma biology.” 2015. Web. 23 Feb 2020.
Vancouver:
Daniel PM. Identification of CREB as a transcriptional regulator of glioblastoma biology. [Internet] [Doctoral dissertation]. University of Melbourne; 2015. [cited 2020 Feb 23].
Available from: http://hdl.handle.net/11343/58851.
Council of Science Editors:
Daniel PM. Identification of CREB as a transcriptional regulator of glioblastoma biology. [Doctoral Dissertation]. University of Melbourne; 2015. Available from: http://hdl.handle.net/11343/58851
University of Manchester
27.
Gu, Muxin.
Functions of histone H2A.Z in regulating transcript levels in budding yeast.
Degree: PhD, 2016, University of Manchester
URL: https://www.research.manchester.ac.uk/portal/en/theses/functions-of-histone-h2az-in-regulating-transcript-levels-in-budding-yeast(06037caf-3b7c-4442-a1f4-b6755fdec250).html
;
http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.713576
► The histone variant H2A.Z is an important regulator of transcription. One unsolved mystery is that why H2A.Z can have both activating and repressive effects on…
(more)
▼ The histone variant H2A.Z is an important regulator of transcription. One unsolved mystery is that why H2A.Z can have both activating and repressive effects on gene expression. By examining both coding and non-coding RNA transcripts in S.cerevisiae, we established that H2A.Z is present at both coding and non-coding promoters and have positive effects on the level of transcripts. The repressive effect of H2A.Z can be partially explained by the sense transcripts of gene being antagonised by H2A.Z-activated antisense transcripts. We also established that H2A.Z-associated non-coding transcripts are predominantly located at bidirectional promoters. The sense and antisense pairs produced from bidirectional promoters show high degrees of coregulation (especially co-activation) during stress response. Surprisingly, we found that the non-coding RNA co-activated with stress-response genes tend to spread the activation signal to the neighbouring gene further upstream, indicating their potential functions in gene regulation. In addition, we also observed that accumulation of H2A.Z at gene promoters is associated with slower recovery from gene induction, which could be related to the Ino80 pathway. In general, our results confirmed the interleaved nature of regulatory system in eukaryotes and highlighted the importance of taking both coding and non-coding transcripts into account while studying the transcriptional regulation.
Subjects/Keywords: 572; H2A.Z; Transcription
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APA ·
Chicago ·
MLA ·
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Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Gu, M. (2016). Functions of histone H2A.Z in regulating transcript levels in budding yeast. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/functions-of-histone-h2az-in-regulating-transcript-levels-in-budding-yeast(06037caf-3b7c-4442-a1f4-b6755fdec250).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.713576
Chicago Manual of Style (16th Edition):
Gu, Muxin. “Functions of histone H2A.Z in regulating transcript levels in budding yeast.” 2016. Doctoral Dissertation, University of Manchester. Accessed February 23, 2020.
https://www.research.manchester.ac.uk/portal/en/theses/functions-of-histone-h2az-in-regulating-transcript-levels-in-budding-yeast(06037caf-3b7c-4442-a1f4-b6755fdec250).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.713576.
MLA Handbook (7th Edition):
Gu, Muxin. “Functions of histone H2A.Z in regulating transcript levels in budding yeast.” 2016. Web. 23 Feb 2020.
Vancouver:
Gu M. Functions of histone H2A.Z in regulating transcript levels in budding yeast. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2020 Feb 23].
Available from: https://www.research.manchester.ac.uk/portal/en/theses/functions-of-histone-h2az-in-regulating-transcript-levels-in-budding-yeast(06037caf-3b7c-4442-a1f4-b6755fdec250).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.713576.
Council of Science Editors:
Gu M. Functions of histone H2A.Z in regulating transcript levels in budding yeast. [Doctoral Dissertation]. University of Manchester; 2016. Available from: https://www.research.manchester.ac.uk/portal/en/theses/functions-of-histone-h2az-in-regulating-transcript-levels-in-budding-yeast(06037caf-3b7c-4442-a1f4-b6755fdec250).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.713576
University of California – Berkeley
28.
Fischer, Jonathan Robert.
Statistical Methods and Analyses in Computational Genomics: Explorations of Eukaryotic Transcription.
Degree: Statistics, 2018, University of California – Berkeley
URL: http://www.escholarship.org/uc/item/1k50v316
► The introduction of next-generation, or high-throughput, sequencing techniques has fundamentally altered our perception of the genome and transcriptome by permitting the simultaneous study of tens…
(more)
▼ The introduction of next-generation, or high-throughput, sequencing techniques has fundamentally altered our perception of the genome and transcriptome by permitting the simultaneous study of tens of thousands of distinct transcripts. In recent years, the popularity of next-generation sequencing has risen due to reductions in costs and the steady accumulation of novel genetic and genomic discoveries which would have proven difficult to uncover with older approaches. The continued proliferation of these techniques both in number and frequency of use has resulted in unique data types and experimental structures which require analysis and frequently methodological development.In this dissertation, I explore eukaryotic transcription from multiple perspectives by applying both classical and novel statistical methods to data generated by different next-generation sequencing protocols. I begin by constructing spatial nascent transcription profiles based on various RNA Polymerase II footprinting procedures to demonstrate the profound deleterious effect of RNA transcript decay factor deletion on mRNA production in yeast, bolsterering and expanding upon prior evidence of the inextricable link between RNA synthesis and decay. My focus then shifts to the development and application of a tensor-based method to RNA-seq data of both the bulk and single-cell varieties. This method is intended for use with data produced in experiments with increasingly-common specially-structured designs in which samples share tissues and/or individuals, and I show that it more robustly and powerfully characterizes the transcriptome via simulation and application to human bulk gene expression measurements. I conclude by employing this method jointly with traditional approaches to investigate the tissue-specific effects on gene expression as measured in murine single-cell RNA-seq and discuss the merits of tensor methods in such a setting.
Subjects/Keywords: Statistics; Tensor; Transcription
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APA (6th Edition):
Fischer, J. R. (2018). Statistical Methods and Analyses in Computational Genomics: Explorations of Eukaryotic Transcription. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/1k50v316
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Fischer, Jonathan Robert. “Statistical Methods and Analyses in Computational Genomics: Explorations of Eukaryotic Transcription.” 2018. Thesis, University of California – Berkeley. Accessed February 23, 2020.
http://www.escholarship.org/uc/item/1k50v316.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Fischer, Jonathan Robert. “Statistical Methods and Analyses in Computational Genomics: Explorations of Eukaryotic Transcription.” 2018. Web. 23 Feb 2020.
Vancouver:
Fischer JR. Statistical Methods and Analyses in Computational Genomics: Explorations of Eukaryotic Transcription. [Internet] [Thesis]. University of California – Berkeley; 2018. [cited 2020 Feb 23].
Available from: http://www.escholarship.org/uc/item/1k50v316.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Fischer JR. Statistical Methods and Analyses in Computational Genomics: Explorations of Eukaryotic Transcription. [Thesis]. University of California – Berkeley; 2018. Available from: http://www.escholarship.org/uc/item/1k50v316
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Duke University
29.
Hamilton, Keri.
Biochemical and Structural Studies on PrfA, the Transcriptional Regulator of Virulence in Listeria monocytogenes
.
Degree: 2016, Duke University
URL: http://hdl.handle.net/10161/12124
► Abstract Listeria monocytogenes is a gram-positive soil saprophytic bacterium that is capable of causing fatal infection in humans. The main virulence regulator PrfA, a…
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▼ Abstract Listeria monocytogenes is a gram-positive soil saprophytic bacterium that is capable of causing fatal infection in humans. The main virulence regulator PrfA, a member of the Crp/FNR family of transcriptional regulators, activates the expression of essential proteins required for host cell invasion and cell-to-cell spread. The mechanism of PrfA activation and the identity of its small molecule coactivator have remained a mystery for more than 20 years, but it is hypothesized that PrfA shares mechanistic similarity to the E. coli cAMP binding protein, Crp. Crp activates gene expression by binding cAMP, increasing the DNA binding affinity of the protein and causing a significant DNA bend that facilitates RNA polymerase binding and downstream gene activation. Our data suggests PrfA activates virulence protein expression through a mechanism distinct from the canonical Crp activation mechanism that involves a combination of cysteine residue reduction and glutathione (GSH) binding. Listeria lacking glutathione synthase (ΔgshF) is avirulent in mice; however virulence is rescued when the bacterium expresses the constitutively active PrfA mutant G145S. Interestingly, Listeria expressing a PrfA mutant in which its four cysteines are mutated to alanine (Quad PrfA), demonstrate a 30-fold decrease in virulence. The Quad and ΔgshF double mutant strains are avirulent. DNA-binding affinity, measured through fluorescence polarization assays, indicate reduction of the cysteine side chains is sufficient to allow PrfA to binds its physiological promoters Phly and PactA with low nanomolar affinity. Oxidized PrfA binds the promoters poorly. Unexpectedly, Quad also binds promoter DNA with nanomolar affinity, suggesting that the cysteines play a role in
transcription efficiency in addition to DNA binding. Both PrfA and Quad bind GSH at physiologically relevant and comparable affinities, however GSH did not affect DNA binding in either case. Thermal denaturation assays suggest that Quad and wild-type PrfA differ structurally upon binding GSH, which supports the in vivo difference in infection between the regulator and its mutant. Structures of PrfA in complex with cognate DNA, determined through X-ray crystallography, further support the disparity between PrfA and Crp activation mechanisms as two structures of reduced PrfA bound to Phly (PrfA-Phly30 and PrfA-Phly24) suggest the DNA adopts a less bent DNA conformation when compared to Crp-cAMP- DNA. The structure of Quad-Phly30 confirms the DNA-binding data as the protein-DNA complex adopts the same overall conformation as PrfA-Phly. From these results, we hypothesize a two-step activation mechanism wherein PrfA, oxidized upon cell entry and unable to bind DNA, is reduced upon its intracellular release and binds DNA, causing a slight bend in the promoter and small increase in
transcription of PrfA-regulated genes. The structures of PrfA-Phly30 and PrfA-Phly24 likely visualize this intermediate complex. Increasing concentrations of…
Advisors/Committee Members: Brennan, Richard G (advisor).
Subjects/Keywords: Biochemistry;
PrfA;
Transcription
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❌
APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hamilton, K. (2016). Biochemical and Structural Studies on PrfA, the Transcriptional Regulator of Virulence in Listeria monocytogenes
. (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/12124
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Hamilton, Keri. “Biochemical and Structural Studies on PrfA, the Transcriptional Regulator of Virulence in Listeria monocytogenes
.” 2016. Thesis, Duke University. Accessed February 23, 2020.
http://hdl.handle.net/10161/12124.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Hamilton, Keri. “Biochemical and Structural Studies on PrfA, the Transcriptional Regulator of Virulence in Listeria monocytogenes
.” 2016. Web. 23 Feb 2020.
Vancouver:
Hamilton K. Biochemical and Structural Studies on PrfA, the Transcriptional Regulator of Virulence in Listeria monocytogenes
. [Internet] [Thesis]. Duke University; 2016. [cited 2020 Feb 23].
Available from: http://hdl.handle.net/10161/12124.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Hamilton K. Biochemical and Structural Studies on PrfA, the Transcriptional Regulator of Virulence in Listeria monocytogenes
. [Thesis]. Duke University; 2016. Available from: http://hdl.handle.net/10161/12124
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Miami
30.
Catoe, Heath W.
The Role of E6-Associated Protein in Estrogen Receptor Alpha Regulation.
Degree: PhD, Biochemistry and Molecular Biology (Medicine), 2010, University of Miami
URL: https://scholarlyrepository.miami.edu/oa_dissertations/464
► The Estrogen Receptor alpha (ER alpha) is a multi-domain transcription factor that has been extensively studied due to its known involvement in breast cancer…
(more)
▼ The Estrogen Receptor alpha (ER alpha) is a multi-domain
transcription factor that has been extensively studied due to its known involvement in breast cancer treatment and progression. Subsequent studies have shown coregulators are extensively involved in modulating the transcriptional activation of ER alpha and many of these proteins possess enzymatic functions. Coregulators are divided into two categories, coactivators which enhance transcriptional output and corepressors which decrease transcriptional output. One protein responsible for Angelman syndrome, E6-associated protein (E6-AP) was found to be a coactivator of ER alpha and possessed ubiquitin ligase activity; however, the ubiquitin ligase activity has been shown not to be essential to E6-AP coactivation ability. The current work was undertaken to explore the role of E6-AP in the regulation of ER alpha. E6-AP was found to play a role in a unique ligand-independent degradation pathway. Because the degradation effect was ligand-independent, it was proposed that the degradation signal mediating the event occurred through phosphorylation of E6-AP. In silico analysis of E6-AP indicated several potential phosphorylation sites on the E6-AP protein. Numerous phosphorylation sites of E6-AP were confirmed by western blot and mass spec indicating a possible phosphorylation signal mediating E6-AP/ER alpha interaction. Because it has been shown that the ligase function of E6-AP is not required for its coactivation, we then examined E6-AP coactivation of ERα in the presence of ligand. One well studied gene TFF-1 (pS2) was examined as a model ERα target gene. Estrogen-mediated
transcription from TFF-1 was decreased with knockdown of E6-AP in both MCF-7 and T47D cell lines. Furthermore, under E6-AP knockdown conditions, ChIP of p300, a known histone acetyl transferase (HAT), indicated a reduced recruitment to the TFF-1 promoter in both cell lines. Interestingly, the reduced recruitment of p300 had a cell specific effect on phosphorylated RNA polymerase II (pRNA pol II) recruitment indicating cell specific functions of E6-AP. Further investigation also found a gene specific effect for E6-AP on pRNA pol II recruitment. The current work provides a new role for E6-AP as a coactivator of ER alpha in the form of a scaffold allowing creation of fully functional
transcription complexes in a gene and cell specific manner.
Advisors/Committee Members: T.K. Harris, Terace Fletcher, Sharon J. Elliot, Zafar Nawaz, Kerry Burnstein.
Subjects/Keywords: Degradation; Ubiquitination; Transcription
Record Details
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Record Details
Similar Records
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Catoe, H. W. (2010). The Role of E6-Associated Protein in Estrogen Receptor Alpha Regulation. (Doctoral Dissertation). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_dissertations/464
Chicago Manual of Style (16th Edition):
Catoe, Heath W. “The Role of E6-Associated Protein in Estrogen Receptor Alpha Regulation.” 2010. Doctoral Dissertation, University of Miami. Accessed February 23, 2020.
https://scholarlyrepository.miami.edu/oa_dissertations/464.
MLA Handbook (7th Edition):
Catoe, Heath W. “The Role of E6-Associated Protein in Estrogen Receptor Alpha Regulation.” 2010. Web. 23 Feb 2020.
Vancouver:
Catoe HW. The Role of E6-Associated Protein in Estrogen Receptor Alpha Regulation. [Internet] [Doctoral dissertation]. University of Miami; 2010. [cited 2020 Feb 23].
Available from: https://scholarlyrepository.miami.edu/oa_dissertations/464.
Council of Science Editors:
Catoe HW. The Role of E6-Associated Protein in Estrogen Receptor Alpha Regulation. [Doctoral Dissertation]. University of Miami; 2010. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/464
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Open Access Theses and Dissertations