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University of Utah
1.
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…
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▼ 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 March 01, 2021.
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. 01 Mar 2021.
Vancouver:
Close DW. Structural and Biochemical Studies of the Transcription Elongation Factors Spt6 and Tex. [Internet] [Doctoral dissertation]. University of Utah; 2010. [cited 2021 Mar 01].
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

Oregon State University
2.
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…
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▼ 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 (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 March 01, 2021.
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. 01 Mar 2021.
Vancouver:
Bhattacharya S. Transcription factor CTIP2 regulates hair follicle development, hair cycling and wound healing. [Internet] [Doctoral dissertation]. Oregon State University; 2014. [cited 2021 Mar 01].
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

Oregon State University
3.
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 ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
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 March 01, 2021.
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. 01 Mar 2021.
Vancouver:
Kyrylkova K. The role of the transcriptional regulatory protein BCL11B in dental and craniofacial development. [Internet] [Doctoral dissertation]. Oregon State University; 2014. [cited 2021 Mar 01].
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

Oregon State University
4.
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 ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
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 March 01, 2021.
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. 01 Mar 2021.
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 2021 Mar 01].
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

University of Ottawa
5.
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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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 March 01, 2021.
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. 01 Mar 2021.
Vancouver:
Hryniuk AK. The Role of Cdx Transcription Factors in the Adult Intestine
. [Internet] [Thesis]. University of Ottawa; 2015. [cited 2021 Mar 01].
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

Portland State University
6.
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 March 01, 2021.
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. 01 Mar 2021.
Vancouver:
Eustis RL. The Role of <i>Pyrococcus furiosus</i> Transcription Factor E in Transcription Iniitiation. [Internet] [Masters thesis]. Portland State University; 2015. [cited 2021 Mar 01].
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

Latrobe University
7.
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 ·
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MLA ·
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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 March 01, 2021.
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. 01 Mar 2021.
Vancouver:
Do HT. Transcription factor binding sites identification using machine learning techniques. [Internet] [Doctoral dissertation]. Latrobe University; 2011. [cited 2021 Mar 01].
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

University of Central Florida
8.
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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Manager
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 March 01, 2021.
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. 01 Mar 2021.
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 2021 Mar 01].
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 Oklahoma
9.
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 ·
Vancouver ·
CSE |
Export
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 March 01, 2021.
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. 01 Mar 2021.
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 2021 Mar 01].
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 Hong Kong
10.
杨澍.
Co-evolution of
transcription factors and their binding sites.
Degree: 2011, University of Hong Kong
URL: http://hdl.handle.net/10722/141941
Subjects/Keywords: Transcription factors.
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
杨澍. (2011). Co-evolution of
transcription factors and their binding sites. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/141941
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
杨澍. “Co-evolution of
transcription factors and their binding sites.” 2011. Thesis, University of Hong Kong. Accessed March 01, 2021.
http://hdl.handle.net/10722/141941.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
杨澍. “Co-evolution of
transcription factors and their binding sites.” 2011. Web. 01 Mar 2021.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Vancouver:
杨澍. Co-evolution of
transcription factors and their binding sites. [Internet] [Thesis]. University of Hong Kong; 2011. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/10722/141941.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
杨澍. Co-evolution of
transcription factors and their binding sites. [Thesis]. University of Hong Kong; 2011. Available from: http://hdl.handle.net/10722/141941
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation

University of Rochester
11.
Balasubramanian, Revathi.
Requirement for LIM-Homeodomain Transcription Factor LHX9
in the Differentiation of Amacrine Cell Subtypes.
Degree: PhD, 2015, University of Rochester
URL: http://hdl.handle.net/1802/29359
► In the mammalian retina, amacrine interneurons are the most diverse group of retinal neurons and contribute to a wide range of visual functions. Amacrine cells…
(more)
▼ In the mammalian retina, amacrine interneurons are
the most diverse group of retinal
neurons and contribute to a wide
range of visual functions. Amacrine cells express
inhibitory
neurotransmitters and can broadly be classified into cells that
either express
gamma-aminobutyric acid or glycine, with each group
being further classified into
different subtypes based on
dendritic morphology, neurotransmitter type expressed and
laminar
stratification at the inner plexiform layer. Understanding the
molecular basis of
genesis of individual amacrine cell subtypes is
crucial for elucidating their visual
functions. Currently, our
understanding of transcriptional regulation affecting the
differentiation of retinal precursor cells into retinal neuron
subtypes is limited. To address
this issue, we identified a
LIM-homeodomain transcription factor – LHX9 that is
expressed in
developing and mature retinal neurons. Specifically, LHX9 is
expressed
predominantly in a subset of GABAergic amacrine
interneurons that express GAD67. We
developed a lineage tracing
strategy by creating an Lhx9-GFP-CreER (Lhx9GCE/+) mouse
line and
crossing to a tdTomato reporter line (RosatdTomato/+), to map the
fate of Lhx9
expressing progenitor cells. We report that in
animals lacking Lhx9, the mature retina
displays aberrant synaptic
lamination at the IPL. We show that this aberration is caused
by
an almost complete ablation of nitric oxide expressing amacrine
cells concurrent with
significantly altered dendritic projection
of Substance P expressing amacrine cells at the
IPL. Our lineage
tracing studies show that Lhx9 expressing retinal progenitors give
rise to
both GAD65 and GAD67 expressing sub-population of
GABAergic amacrine cells and a
small subset of AII glycinergic
amacrine cells. Taken together, our studies have identified
Lhx9
as a unique molecular marker for a subtype of amacrine cells. Our
studies also show
that Lhx9 is necessary for the development of
nitric oxide-expressing amacrine subtype
population and indicate
that it also plays a significant role in the development of
dendritic
stratification of amacrine cell
subtypes.
Subjects/Keywords: Transcription Factors; Retina; Development
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Balasubramanian, R. (2015). Requirement for LIM-Homeodomain Transcription Factor LHX9
in the Differentiation of Amacrine Cell Subtypes. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/29359
Chicago Manual of Style (16th Edition):
Balasubramanian, Revathi. “Requirement for LIM-Homeodomain Transcription Factor LHX9
in the Differentiation of Amacrine Cell Subtypes.” 2015. Doctoral Dissertation, University of Rochester. Accessed March 01, 2021.
http://hdl.handle.net/1802/29359.
MLA Handbook (7th Edition):
Balasubramanian, Revathi. “Requirement for LIM-Homeodomain Transcription Factor LHX9
in the Differentiation of Amacrine Cell Subtypes.” 2015. Web. 01 Mar 2021.
Vancouver:
Balasubramanian R. Requirement for LIM-Homeodomain Transcription Factor LHX9
in the Differentiation of Amacrine Cell Subtypes. [Internet] [Doctoral dissertation]. University of Rochester; 2015. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/1802/29359.
Council of Science Editors:
Balasubramanian R. Requirement for LIM-Homeodomain Transcription Factor LHX9
in the Differentiation of Amacrine Cell Subtypes. [Doctoral Dissertation]. University of Rochester; 2015. Available from: http://hdl.handle.net/1802/29359

University of Utah
12.
Seidel, Jeffrey John.
Functions of the pointed domain within the ETS gene family;.
Degree: PhD, Oncological Sciences;, 2001, University of Utah
URL: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/342/rec/554
► All members of the ets family of transcription factors conserve the DNA binding ETS domain that recognizes the core sequence 5’-GGA(A/T)-3’. Despite conserving this domain,…
(more)
▼ All members of the ets family of transcription factors conserve the DNA binding ETS domain that recognizes the core sequence 5’-GGA(A/T)-3’. Despite conserving this domain, individual ets proteins can perform specific functions. Many unique features exist among ets proteins that establish this diversity. One feature, the Pointed (PNT) domain, is a region of 80 amino acids conserved among only a subset of ets proteins. The function of the PNT domain is not clear, but it is proposed to mediate hemotypic and heterotypic protein-protein interactions. This thesis investigates the function of the PNT domain of four ets proteins. Surprisingly, this domain was found to serve different functions within the family. First, PNT domains can have different oligomeriazation states. The Fts-1 PNT domain, composed of five alph helices that assume a globular fold, is monomeric in solution. In contrast, the PNT domain of the ets family member TEL formed multimers under a variety of in vitro conditions. Second, PNT domains have different protein partners. In an affinity chromatography experiment, a fragments of Ets-1 spanning the PNT domain an MAPK site bound the mitogen-activated protein kinases (MAPKs) ERK1 and/or ERK2. These kinases phosphorylate Ets-1 and Ets-2 at a MAPK site N-terminal to the PNT domain. Kinase assays identified docking site on the surface of the PNT domain of Ets-1 important for interacting with ERK2 and Ras/MAPK signaling. The docking site is conserved in sequence and in function in the PNT domain of Ets-2 but not in the PNT domain of the ets family member GABPalph. The docking site sequence is also not well-conserved in other PNT domains. These results highlight the PNT domain as a conserved structureal element whose distinct surface features generate specificity of function among ets proteins.
Subjects/Keywords: Transcription Factors
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Seidel, J. J. (2001). Functions of the pointed domain within the ETS gene family;. (Doctoral Dissertation). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/342/rec/554
Chicago Manual of Style (16th Edition):
Seidel, Jeffrey John. “Functions of the pointed domain within the ETS gene family;.” 2001. Doctoral Dissertation, University of Utah. Accessed March 01, 2021.
http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/342/rec/554.
MLA Handbook (7th Edition):
Seidel, Jeffrey John. “Functions of the pointed domain within the ETS gene family;.” 2001. Web. 01 Mar 2021.
Vancouver:
Seidel JJ. Functions of the pointed domain within the ETS gene family;. [Internet] [Doctoral dissertation]. University of Utah; 2001. [cited 2021 Mar 01].
Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/342/rec/554.
Council of Science Editors:
Seidel JJ. Functions of the pointed domain within the ETS gene family;. [Doctoral Dissertation]. University of Utah; 2001. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd1/id/342/rec/554

University of Alberta
13.
Strungaru, Marcela Hermina.
Investigation of the role of PITX2 in ocular expression
pathways and human disease.
Degree: PhD, Medical Sciences - Medical Genetics, 2010, University of Alberta
URL: https://era.library.ualberta.ca/files/v405sb16r
► The overall goal of my work has been to gain a better understanding of Axenfeld-Rieger Syndrome (ARS), a human autosomal dominantly inherited mal-development of the…
(more)
▼ The overall goal of my work has been to gain a better
understanding of Axenfeld-Rieger Syndrome (ARS), a human autosomal
dominantly inherited mal-development of the anterior segment of the
eye that is associated with glaucoma. By studying rare genetic
causes of this complex disease we are gaining insight into the
initial steps that ultimately lead to blindness. To achieve the
goal of better understanding ARS, my research project had two
parts. In the first part, I performed a retrospective clinical
study in which I analyzed the glaucoma-related clinical
presentation of ARS patients with FOXC1 and PITX2 defects. This
study showed a good genotype-phenotype correlation which may be
important for the physician in dealing with ARS patients. Patients
with FOXC1 mutations had the mildest prognosis in glaucoma
development, while patients with PITX2 defects and patients with
FOXC1 duplication had a more severe prognosis in glaucoma
development than patients with FOXC1 mutations. I tried to
determine the best treatment for glaucoma in these patients.
Unfortunately, in this study, current medical therapies did not
successfully lower intraocular pressure or prevent progression of
glaucoma in ARS patients with FOXC1 or PITX2 alterations. This
clinical study also provided useful diagnostic criteria to identify
the gene responsible for ARS. The second part of the project was to
study the gene regulatory pathways of the PITX2 gene, mutations of
which cause ARS. PITX2 is a transcription factor that regulates the
expression of genes in the eye. The discovery of direct downstream
targets of PITX2 is necessary for understanding the genetic
mechanisms underlying complex, highly regulated processes such as
development and underlying heritable human disorders. To find
direct target genes of PITX2, I have used a recently developed
method: the hormone receptor (HR)-inducible expression system for
transcription factors coupled microarray analysis. The results
obtained using this method have involved PITX2 in control of
cellular stress. Recent investigations have suggested significant
roles for cellular stress in glaucoma pathology. Understanding the
control of these key aspects of cell function will have profound
implications for understanding and treating the glaucoma that is
the most clinically serious consequence of mutations of
PITX2.
Subjects/Keywords: Glaucoma, Transcription Factors, Genes
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Strungaru, M. H. (2010). Investigation of the role of PITX2 in ocular expression
pathways and human disease. (Doctoral Dissertation). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/v405sb16r
Chicago Manual of Style (16th Edition):
Strungaru, Marcela Hermina. “Investigation of the role of PITX2 in ocular expression
pathways and human disease.” 2010. Doctoral Dissertation, University of Alberta. Accessed March 01, 2021.
https://era.library.ualberta.ca/files/v405sb16r.
MLA Handbook (7th Edition):
Strungaru, Marcela Hermina. “Investigation of the role of PITX2 in ocular expression
pathways and human disease.” 2010. Web. 01 Mar 2021.
Vancouver:
Strungaru MH. Investigation of the role of PITX2 in ocular expression
pathways and human disease. [Internet] [Doctoral dissertation]. University of Alberta; 2010. [cited 2021 Mar 01].
Available from: https://era.library.ualberta.ca/files/v405sb16r.
Council of Science Editors:
Strungaru MH. Investigation of the role of PITX2 in ocular expression
pathways and human disease. [Doctoral Dissertation]. University of Alberta; 2010. Available from: https://era.library.ualberta.ca/files/v405sb16r

Oregon State University
14.
Bredeweg, Erin L.
Transcriptional networks controlled by the fatty acid regulators FAR-1 and FAR-2.
Degree: PhD, Molecular and Cellular Biology, 2014, Oregon State University
URL: http://hdl.handle.net/1957/46468
► Fungi are capable of growth on a wide variety of carbon sources, both living and dead. They can produce an arsenal of enzymes and transporters…
(more)
▼ Fungi are capable of growth on a wide variety of carbon sources, both living and dead. They can produce an arsenal of enzymes and transporters for harvesting sugars, polysaccharides, amino acids, lipids and micronutrients from their environments [1]. Within the nucleus of a cell,
transcription factors (TF) control whether genes will be transcribed, after which the transcripts can be translated into functional protein. TF contact with DNA can be influenced by nucleosomal occupancy, DNA binding affinity, and competition with other DNA binding proteins [2], [3]. Sequence specific DNA binding
transcription factors associate with promoter sequences in order to tune core metabolic pathways in response to nutrient availability, for example N. crassa’s major nitrogen regulator NIT-2, [4], or in response to oxidative stress, the alternative oxidase regulator, AOD-2 [5]. Change in the relative abundance of proteins within the cell or "proteome" can have broad effects from redirection of metabolic flux via carbon and nitrogen use, production of enzymes for detoxification, and altered growth and development from the examples above. A survey of
transcription factor binding influenced by light is underway in Neurospora crassa as part of the Neurospora Functional Genomics and Systems Biology (NcFGSB) program project funded by the NIH (P01GM). This work began by testing the link of FAR-1, or Fatty Acid Regulator -1 (NCU08000) to light regulation, but has continued toward investigation of how both FAR-1 and a second TF, Fatty Acid Regulator-2, or FAR-2 (NCU03643) influence central metabolism, oxidative stress response, and development.
Transcription factor networks consist of describing TFs that bind to multiple genes and individual genes controlled by multiple regulators. Further, the "regulation of regulators" describes how the
transcription of
transcription factor genes is controlled. Chromatin immunoprecipitation, or 'ChIP' experiments show that a variety of
factors are enriched at the same promoter region as can be seen by comparing multiple datasets [6], [7]. Transcriptional regulators may promote or inhibit one another from binding DNA, leading to a total regulation as the sum of TF activity. This complexity cannot be explained by single genetic experiments and study of a limited number of loci. Even in the event of TF association with specific promoter DNA as analyzed by ChIP, proximal binding of a transcriptional activator does not directly mean that transcript levels will increase, as we have seen with the identification of WC-2 binding sites [7].
I used a reverse genetics approach, assaying deletion mutants of selected loci, to determine the cellular effects of FAR-1 and FAR-2 transcriptional activity in different carbon sources. The tools of high throughput sequencing, and bioinformatics data analyses were combined with experiments to characterize phenotypes observed. Here I report (1) a collection of binding sites found in the Neurospora genome for FAR-1 and FAR-2 in sucrose, butyrate, and oleate, (2) changes in…
Advisors/Committee Members: Freitag, Michael (advisor), Taylor, Barbara (committee member).
Subjects/Keywords: fatty acid; Transcription factors
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bredeweg, E. L. (2014). Transcriptional networks controlled by the fatty acid regulators FAR-1 and FAR-2. (Doctoral Dissertation). Oregon State University. Retrieved from http://hdl.handle.net/1957/46468
Chicago Manual of Style (16th Edition):
Bredeweg, Erin L. “Transcriptional networks controlled by the fatty acid regulators FAR-1 and FAR-2.” 2014. Doctoral Dissertation, Oregon State University. Accessed March 01, 2021.
http://hdl.handle.net/1957/46468.
MLA Handbook (7th Edition):
Bredeweg, Erin L. “Transcriptional networks controlled by the fatty acid regulators FAR-1 and FAR-2.” 2014. Web. 01 Mar 2021.
Vancouver:
Bredeweg EL. Transcriptional networks controlled by the fatty acid regulators FAR-1 and FAR-2. [Internet] [Doctoral dissertation]. Oregon State University; 2014. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/1957/46468.
Council of Science Editors:
Bredeweg EL. Transcriptional networks controlled by the fatty acid regulators FAR-1 and FAR-2. [Doctoral Dissertation]. Oregon State University; 2014. Available from: http://hdl.handle.net/1957/46468

Texas A&M University
15.
Hedrick, Erik Duane.
Diindolylmethane Analogs as Novel NR4A1 Antagonists and as a Novel Class of Anticancer Agents and Sp Transcription Factors as Nononcogene Addiction Genes That Are Targets of ROS Inducing Agents.
Degree: PhD, Toxicology, 2016, Texas A&M University
URL: http://hdl.handle.net/1969.1/159116
► The orphan nuclear receptor 4A1 (NR4A1) and specificity protein (Sp) transcription factors (TFs) are both overexpressed in the majority of solid tumors. Our laboratory has…
(more)
▼ The orphan nuclear receptor 4A1 (NR4A1) and specificity protein (Sp)
transcription factors (TFs) are both overexpressed in the majority of solid tumors. Our laboratory has researched the molecular mechanisms of a novel class of 1,1-bis(3'-indolyl)-1-(p-substituted phenyl)methanes (C-DIMs) as NR4A1 antagonists and Sp proteins as non-oncogene addiction genes (NOA) that are targets of reactive oxygen species (ROS) inducing agents. Nr4A1 antagonists (DIM-C-pPhOH) (C-DIM 8) and (DIM-C-pPhCO2Me) (C-DIM 14) inhibited cancer cell proliferation, induced apoptosis, and inhibited migration. The NR4A1 antagonists inhibited constitutive and TGFβ-induced migration in Triple Negative Breast Cancer (TNBC) cells. We also demonstrate that p38α is necessary and sufficient for TGFβ-mediated migration and NR4A1 nuclear export in triple negative breast cancer (TNBC) which was attenuated with NR4A1 antagonists (C-DIMs), leptomycin B, and the p38 inhibitor SB202190. We also demonstrate that NR4A1 is essential for TGFβ-induced EMT and NR4A1 antagonists promoted cytosolic sequestration of the
transcription factor β-catenin and its proteasome-dependent degradation in a time dependent manner. β-catenin, along with TCF-3, TCF-4, and LEF-1 binds to TCF/LEF response elements in the NR4A1 promoter, regulating its expression.
RNA interference (RNAi) demonstrates that Sp1, 3, and 4 TFs individually play a role in cancer cell growth, survival and migration/invasion in cancer cell lines. Individual knockdown of Sp1, Sp3, or Sp4, resulted in inhibition of cell growth, migration, and induction of apoptosis, with no compensation. Moreover, tumor growth in athymic nude mice bearing pancreatic cancer xenografts was significantly attenuated in cells depleted of Sp1, Sp3, and Sp4 in combination or Sp1 alone. Ingenuity Pathway Analysis (IPA) of changes in gene expression in Panc1 pancreatic cancer cells after individual knockdown of Sp TFs demonstrates that Sp1-, Sp3- and Sp4-regulated genes were associated with pro-oncogenic activity.
C-DIMs are promising anticancer agents in NR4A1-overexpressing solid tumors and represent a novel class of mechanistic-based drugs that target TGFβ/NR4A1-dependent inducible migration in TNBC. The functional and genomic results coupled with overexpression of Sp
transcription factors in tumor vs. non-tumor tissues and decreased Sp1 expression with age indicate that Sp1, Sp3 and Sp4 are non-oncogene addiction (NOA) genes and are attractive drug targets for individual and combined cancer chemotherapies.
Advisors/Committee Members: Safe, Stephen H (advisor), Burghardt, Robert C (committee member), Phillips, Timothy D (committee member), Tian, Yanan (committee member).
Subjects/Keywords: NR4A1; Sp transcription factors
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hedrick, E. D. (2016). Diindolylmethane Analogs as Novel NR4A1 Antagonists and as a Novel Class of Anticancer Agents and Sp Transcription Factors as Nononcogene Addiction Genes That Are Targets of ROS Inducing Agents. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/159116
Chicago Manual of Style (16th Edition):
Hedrick, Erik Duane. “Diindolylmethane Analogs as Novel NR4A1 Antagonists and as a Novel Class of Anticancer Agents and Sp Transcription Factors as Nononcogene Addiction Genes That Are Targets of ROS Inducing Agents.” 2016. Doctoral Dissertation, Texas A&M University. Accessed March 01, 2021.
http://hdl.handle.net/1969.1/159116.
MLA Handbook (7th Edition):
Hedrick, Erik Duane. “Diindolylmethane Analogs as Novel NR4A1 Antagonists and as a Novel Class of Anticancer Agents and Sp Transcription Factors as Nononcogene Addiction Genes That Are Targets of ROS Inducing Agents.” 2016. Web. 01 Mar 2021.
Vancouver:
Hedrick ED. Diindolylmethane Analogs as Novel NR4A1 Antagonists and as a Novel Class of Anticancer Agents and Sp Transcription Factors as Nononcogene Addiction Genes That Are Targets of ROS Inducing Agents. [Internet] [Doctoral dissertation]. Texas A&M University; 2016. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/1969.1/159116.
Council of Science Editors:
Hedrick ED. Diindolylmethane Analogs as Novel NR4A1 Antagonists and as a Novel Class of Anticancer Agents and Sp Transcription Factors as Nononcogene Addiction Genes That Are Targets of ROS Inducing Agents. [Doctoral Dissertation]. Texas A&M University; 2016. Available from: http://hdl.handle.net/1969.1/159116

Texas A&M University
16.
Malapi-Wight, Martha Maria.
The Role of Cys2-His2 Zinc Finger Transcription Factors in Polyol Metabolism, Asexual Development and Fumonisin Biosynthesis in Fusarium verticillioides.
Degree: PhD, Plant Pathology, 2013, Texas A&M University
URL: http://hdl.handle.net/1969.1/149477
► The ascomycete Fusarium verticillioides (Sacc.) Nirenberg (teleomorph: Gibberella moniliformis Wineland) causes stalk and ear rots on maize worldwide. In addition to the economic losses due…
(more)
▼ The ascomycete Fusarium verticillioides (Sacc.) Nirenberg (teleomorph: Gibberella moniliformis Wineland) causes stalk and ear rots on maize worldwide. In addition to the economic losses due to reduced yield, the fungus produces fumonisins on infected corn. One of the unanswered questions in mycotoxin research is how fungi perceive and respond to various extracellular stimuli and produce mycotoxins. To date, extensive research has been performed on important signaling pathways that regulate mycotoxin biosynthesis, but little is known about the downstream target genes, notably
transcription factors (TFs). While the roles of TFs have shown to be critical in eukaryotic
transcription regulation, only a few have been characterized in F. verticillioides. TFs with zinc fingers have been reported in all living organisms, and in fungal species, members of the Cys2-Hys2 (C2H2) zinc finger TF family are predicted to be involved in cell differentiation, carbon utilization, and development. Using the available genomic resources, I constructed a library of C2H2 TF deletion mutants, and identified SDA1, FvFLBC and CHT1 genes with a potential role in carbon utilization, development and fumonisin B1 (FB1) biosynthesis. The Δsda1 strain showed complete growth inhibition when using sorbitol as the sole carbon source and produced higher levels of FB1 when grown on corn kernels. In addition, the Δsda1 strain produced less number of conidia compared to the wild-type progenitor. Through gene complementation, I also demonstrated that F. verticillioides SDA1 and Trichoderma reesei ACE1 are functionally conserved. FvFLBC acts as a regulator of asexual development but not FB1 biosynthesis. I also discovered that the FvFlbC N-terminus is critical for conidia production. CHT1 is associated with asexual development, fumonisin biosynthesis and pigmentation. Characterization of key signal transduction pathways, and more importantly the function of SDA1, FvFLBC and CHT1, should facilitate the elucidation of the mechanisms and regulations of growth, development, and secondary metabolism in F. verticillioides. The outcome of this study may help us determine how to minimize F. verticillioides contamination of crops and the resulting mycotoxins, providing safer and higher value corn in the US and worldwide.
Advisors/Committee Members: Shim, Won-Bo (advisor), He, Ping (committee member), Shaw, Brian D (committee member), Scholthof, Herman B (committee member).
Subjects/Keywords: Fusarium verticillioides; transcription factors
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APA ·
Chicago ·
MLA ·
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APA (6th Edition):
Malapi-Wight, M. M. (2013). The Role of Cys2-His2 Zinc Finger Transcription Factors in Polyol Metabolism, Asexual Development and Fumonisin Biosynthesis in Fusarium verticillioides. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/149477
Chicago Manual of Style (16th Edition):
Malapi-Wight, Martha Maria. “The Role of Cys2-His2 Zinc Finger Transcription Factors in Polyol Metabolism, Asexual Development and Fumonisin Biosynthesis in Fusarium verticillioides.” 2013. Doctoral Dissertation, Texas A&M University. Accessed March 01, 2021.
http://hdl.handle.net/1969.1/149477.
MLA Handbook (7th Edition):
Malapi-Wight, Martha Maria. “The Role of Cys2-His2 Zinc Finger Transcription Factors in Polyol Metabolism, Asexual Development and Fumonisin Biosynthesis in Fusarium verticillioides.” 2013. Web. 01 Mar 2021.
Vancouver:
Malapi-Wight MM. The Role of Cys2-His2 Zinc Finger Transcription Factors in Polyol Metabolism, Asexual Development and Fumonisin Biosynthesis in Fusarium verticillioides. [Internet] [Doctoral dissertation]. Texas A&M University; 2013. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/1969.1/149477.
Council of Science Editors:
Malapi-Wight MM. The Role of Cys2-His2 Zinc Finger Transcription Factors in Polyol Metabolism, Asexual Development and Fumonisin Biosynthesis in Fusarium verticillioides. [Doctoral Dissertation]. Texas A&M University; 2013. Available from: http://hdl.handle.net/1969.1/149477

University of Texas Southwestern Medical Center
17.
Renthal, Nora Edwards.
Post-Transcriptional Regulation by microRNAS in Pregnancy and Parturition.
Degree: 2012, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/1113
► Throughout most of pregnancy, uterine quiescence is maintained by increased progesterone receptor (PR) transcriptional activity, while spontaneous labor is initiated/facilitated by a concerted series of…
(more)
▼ Throughout most of pregnancy, uterine quiescence is maintained by increased progesterone receptor (PR) transcriptional activity, while spontaneous labor is initiated/facilitated by a concerted series of biochemical events that activate inflammatory pathways and negatively impact PR function. In this study, we uncovered a new regulatory pathway whereby miRNAs serve as hormonally-modulated and conserved mediators of contractile gene regulation in the pregnant uterus from mouse to human. Using miRNA and gene expression microarray analyses of uterine tissues, we identified a conserved family of miRNAs, the miR-200 family, that is highly induced at term in both mice and humans, as well as two coordinately downregulated targets, zinc finger E-box binding homeobox proteins, ZEB1 and ZEB2, which act as transcriptional repressors. We also observed upregulation of the miR-200 family and downregulation of ZEB1 and ZEB2 in two different mouse models of preterm labor. We further demonstrated that ZEB1 is directly upregulated by the action of P4/PR at the ZEB1 promoter. Excitingly, we observed that ZEB1 and ZEB2 inhibited expression of the contraction-associated genes, oxytocin receptor and connexin-43 and blocked oxytocin-induced contractility in human myometrial cells. Together, these findings implicate the miR-200 family and their targets ZEB1 and ZEB2 as novel P4/PR-mediated regulators of uterine quiescence and contractility during pregnancy and labor, and shed new light on the molecular mechanisms involved in preterm birth.
Advisors/Committee Members: Mendelson, Carole R..
Subjects/Keywords: Labor, Obstetric; MicroRNAs; Transcription Factors
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Chicago ·
MLA ·
Vancouver ·
CSE |
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to Zotero / EndNote / Reference
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APA (6th Edition):
Renthal, N. E. (2012). Post-Transcriptional Regulation by microRNAS in Pregnancy and Parturition. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1113
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):
Renthal, Nora Edwards. “Post-Transcriptional Regulation by microRNAS in Pregnancy and Parturition.” 2012. Thesis, University of Texas Southwestern Medical Center. Accessed March 01, 2021.
http://hdl.handle.net/2152.5/1113.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Renthal, Nora Edwards. “Post-Transcriptional Regulation by microRNAS in Pregnancy and Parturition.” 2012. Web. 01 Mar 2021.
Vancouver:
Renthal NE. Post-Transcriptional Regulation by microRNAS in Pregnancy and Parturition. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2012. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/2152.5/1113.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Renthal NE. Post-Transcriptional Regulation by microRNAS in Pregnancy and Parturition. [Thesis]. University of Texas Southwestern Medical Center; 2012. Available from: http://hdl.handle.net/2152.5/1113
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Columbia University
18.
Borok, Matthew Jay.
New Perspectives on Gata Redundancy in Mouse Embryogenesis.
Degree: 2015, Columbia University
URL: https://doi.org/10.7916/D8S181WM
► Gata4 and Gata6 are closely related transcription factors that are essential for the development of a number of embryonic tissues. While they have nearly identical…
(more)
▼ Gata4 and Gata6 are closely related transcription factors that are essential for the development of a number of embryonic tissues. While they have nearly identical DNA-binding domains and similar patterns of expression, Gata4 and Gata6 null embryos have strikingly different embryonic lethal phenotypes. Conditional deletion of these genes in the pancreas has also revealed specific functions for each factor in this organ. To investigate the role of these genes in pancreatic development, we performed a number of biochemical experiments on pancreatic cell lines and mutant tissues. We found that Gata4 and Gata6 regulate overlapping sets of genes in the developing pancreas. To determine whether the lack of global redundancy between Gata4 and Gata6 is due to differences in protein function or Gata4 and Gata6 expression domains, we generated mice that contained the Gata6 cDNA in place of the Gata4 genomic locus. Gata4Gata6/Gata6 embryos survived through embryonic day (e)12.5 and successfully underwent ventral folding morphogenesis, demonstrating that Gata6 is able to replace Gata4 function in extraembryonic tissues. Interestingly, Gata6 is unable to replace Gata4 function in the septum transversum mesenchyme or the epicardium, leading to liver agenesis and lethal heart defects in Gata4Gata6/Gata6 embryos. These studies suggest that Gata4 has evolved distinct functions in the development of these tissues that cannot be performed by Gata6, even when it is provided in the identical expression domain. Our work has important implications for the respective mechanisms of Gata function during development, as well as the functional evolution of these essential transcription factors.
Subjects/Keywords: Transcription factors; Pancreas; Embryology; Genetics
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Borok, M. J. (2015). New Perspectives on Gata Redundancy in Mouse Embryogenesis. (Doctoral Dissertation). Columbia University. Retrieved from https://doi.org/10.7916/D8S181WM
Chicago Manual of Style (16th Edition):
Borok, Matthew Jay. “New Perspectives on Gata Redundancy in Mouse Embryogenesis.” 2015. Doctoral Dissertation, Columbia University. Accessed March 01, 2021.
https://doi.org/10.7916/D8S181WM.
MLA Handbook (7th Edition):
Borok, Matthew Jay. “New Perspectives on Gata Redundancy in Mouse Embryogenesis.” 2015. Web. 01 Mar 2021.
Vancouver:
Borok MJ. New Perspectives on Gata Redundancy in Mouse Embryogenesis. [Internet] [Doctoral dissertation]. Columbia University; 2015. [cited 2021 Mar 01].
Available from: https://doi.org/10.7916/D8S181WM.
Council of Science Editors:
Borok MJ. New Perspectives on Gata Redundancy in Mouse Embryogenesis. [Doctoral Dissertation]. Columbia University; 2015. Available from: https://doi.org/10.7916/D8S181WM

Hong Kong University of Science and Technology
19.
Jia, Huiqiang.
Dynamics of mitochondrial RNA polymerase transcription elongation in the presence of DNA damage and the effect of transcription factors.
Degree: 2016, Hong Kong University of Science and Technology
URL: http://repository.ust.hk/ir/Record/1783.1-87117
;
https://doi.org/10.14711/thesis-b1626253
;
http://repository.ust.hk/ir/bitstream/1783.1-87117/1/th_redirect.html
► As the first step of gene expression, accurate transcription is essential to keep normal translation and the functions of proteins. Human mitochondrial RNA polymerase (POLRMT,…
(more)
▼ As the first step of gene expression, accurate transcription is essential to keep normal translation and the functions of proteins. Human mitochondrial RNA polymerase (POLRMT, for short), which exists in human mitochondria, is responsible for transcription of 13 subunits of the oxidative phosphorylation complexes, 2 ribosomal RNAs (rRNAs) and 22 transfer RNAs (tRNAs). POLRMT has the highest sequence similarity to bacteriophage T7 RNA polymerase, although it seems that the transcription elongation mechanism of POLRMT is much similar to that of nucleus RNA polymerase II (Pol II). In fact, there are also a few differences between the mitochondrial and the nucleus transcription elongations. First, distinct transcription elongation factors are present in mitochondria. For example, TEFM (transcription elongation factor, mitochondria), which is a unique transcription factor in mitochondria can facilitate transcription elongation by interacting with POLRMT elongation complex. Second, mitochondrial DNA is more susceptible to DNA damages due to lack of nucleosome as well as of certain DNA repair mechanisms. Therefore, POLRMT has to go through damaged DNA more frequently. Here, we study the effects of DNA damages and transcription factors on mitochondrial transcription elongation. We found that POLRMT stalls at the Cisplatin and 8-oxoguanine DNA damage sites and some of these pauses/stalls can be enhanced by TFAM (transcription repression factor) and can be rescued by TEFM. We will expand these finding to understand the transcription elongation dynamics of POLRMT in the presence of DNA damages as well as mitochondrial transcription elongation factors by single-molecule and real-time machine – optical tweezers. Key words: POLRMT, Transcription Elongation, Transcription Factors, Optical Tweezers, Dynamics
Subjects/Keywords: RNA polymerases
; Transcription factors
; Mitochondria
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Jia, H. (2016). Dynamics of mitochondrial RNA polymerase transcription elongation in the presence of DNA damage and the effect of transcription factors. (Thesis). Hong Kong University of Science and Technology. Retrieved from http://repository.ust.hk/ir/Record/1783.1-87117 ; https://doi.org/10.14711/thesis-b1626253 ; http://repository.ust.hk/ir/bitstream/1783.1-87117/1/th_redirect.html
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):
Jia, Huiqiang. “Dynamics of mitochondrial RNA polymerase transcription elongation in the presence of DNA damage and the effect of transcription factors.” 2016. Thesis, Hong Kong University of Science and Technology. Accessed March 01, 2021.
http://repository.ust.hk/ir/Record/1783.1-87117 ; https://doi.org/10.14711/thesis-b1626253 ; http://repository.ust.hk/ir/bitstream/1783.1-87117/1/th_redirect.html.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Jia, Huiqiang. “Dynamics of mitochondrial RNA polymerase transcription elongation in the presence of DNA damage and the effect of transcription factors.” 2016. Web. 01 Mar 2021.
Vancouver:
Jia H. Dynamics of mitochondrial RNA polymerase transcription elongation in the presence of DNA damage and the effect of transcription factors. [Internet] [Thesis]. Hong Kong University of Science and Technology; 2016. [cited 2021 Mar 01].
Available from: http://repository.ust.hk/ir/Record/1783.1-87117 ; https://doi.org/10.14711/thesis-b1626253 ; http://repository.ust.hk/ir/bitstream/1783.1-87117/1/th_redirect.html.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Jia H. Dynamics of mitochondrial RNA polymerase transcription elongation in the presence of DNA damage and the effect of transcription factors. [Thesis]. Hong Kong University of Science and Technology; 2016. Available from: http://repository.ust.hk/ir/Record/1783.1-87117 ; https://doi.org/10.14711/thesis-b1626253 ; http://repository.ust.hk/ir/bitstream/1783.1-87117/1/th_redirect.html
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Melbourne
20.
GILAN, OMER.
Unravelling the nature of Fra-1 complexes in invasive tumour cells.
Degree: 2012, University of Melbourne
URL: http://hdl.handle.net/11343/38029
► The local and distant spread of tumours in the body through invasion and metastasis are the leading causes of cancer-related deaths. These processes often require…
(more)
▼ The local and distant spread of tumours in the body through invasion and metastasis are the leading causes of cancer-related deaths. These processes often require the remodeling of gene expression, mediated by key transcription factors acting in signalling pathways that are aberrantly activated in tumours. There is now strong evidence that the spread of some epithelial cancers can involve a switch to an invasive mesenchymal phenotype via a process closely related to the epithelial-mesenchymal transition (EMT) that occurs during development.
In colorectal cancer (CRC), pathological EMT is associated with tumour budding at the invasive front of tumours. Several pathways have been implicated in regulating EMT events in cancers, including TGF, Wnt and Ras signalling, but the key transcriptional mediators of EMT programs in CRC cells are not well understood. Recent work in our laboratory has identified a critical role for the Activator Protein-1 (AP-1) transcription factor complex in this process. This complex consists of a dimeric core, formed mainly by members of the Fos, Jun and ATF protein families. We specifically found that the Fos related antigen-1 (Fra-1), a Fos family protein that is over-expressed in response to oncogenic Ras-ERK MAPK activation, directly binds and regulates a clinically relevant cohort of EMT-associated genes, and that Fra-1 is enriched in tumour buds at the invasive front of CRCs. However, the mechanism(s) regulating Fra-1/AP-1 function, including the control of genes involved in CRC cell migration, invasion and EMT remains elusive. We hypothesized that a better understanding of these issue could be gained through analysis of the Fra-1/AP-1 interactome in CRC cells, given the pervasive role that protein-protein interactions play in transcriptional regulation.
A proteomic screen for such interactions in highly invasive CRC cells revealed the existence of heterogenous pools of Fra-1, formed through interaction with different Jun isoforms. The analysis also identified a multitude of novel putative Fra-1 interacting proteins in these cells, which were tentatively placed into two groups. The first included potential Fra-1/AP-1 regulators acting at the signalling level via effects on protein turnover, localisation and post-translational modification. By contrast, the second group consisted of proteins known to associate with chromatin and regulate gene expression. A representative Fra-1/AP-1 interactor from each group was then chosen for further functional characterisation.
Phosphorylation is a central mechanism for regulation of AP-1 protein function. Fra-1 was found to associate with a heterotrimeric protein phosphatase 2A (PP2A) complex consisting of a catalytic subunit (PP2Acat), the PR65 scaffold, and the PR55 regulatory subunit. The latter demonstrated preferential binding to Fra-1/c-Jun but not c-Fos/c-Jun dimers, and was required for recruitment of…
Subjects/Keywords: Invasion; AP-1; transcription factors
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
GILAN, O. (2012). Unravelling the nature of Fra-1 complexes in invasive tumour cells. (Doctoral Dissertation). University of Melbourne. Retrieved from http://hdl.handle.net/11343/38029
Chicago Manual of Style (16th Edition):
GILAN, OMER. “Unravelling the nature of Fra-1 complexes in invasive tumour cells.” 2012. Doctoral Dissertation, University of Melbourne. Accessed March 01, 2021.
http://hdl.handle.net/11343/38029.
MLA Handbook (7th Edition):
GILAN, OMER. “Unravelling the nature of Fra-1 complexes in invasive tumour cells.” 2012. Web. 01 Mar 2021.
Vancouver:
GILAN O. Unravelling the nature of Fra-1 complexes in invasive tumour cells. [Internet] [Doctoral dissertation]. University of Melbourne; 2012. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/11343/38029.
Council of Science Editors:
GILAN O. Unravelling the nature of Fra-1 complexes in invasive tumour cells. [Doctoral Dissertation]. University of Melbourne; 2012. Available from: http://hdl.handle.net/11343/38029

University of Hong Kong
21.
Ho, Ming-how.
Sequence variation and
covariation in forkhead domains.
Degree: 2002, University of Hong Kong
URL: http://hdl.handle.net/10722/28162
Subjects/Keywords: Transcription factors.
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ho, M. (2002). Sequence variation and
covariation in forkhead domains. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/28162
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):
Ho, Ming-how. “Sequence variation and
covariation in forkhead domains.” 2002. Thesis, University of Hong Kong. Accessed March 01, 2021.
http://hdl.handle.net/10722/28162.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ho, Ming-how. “Sequence variation and
covariation in forkhead domains.” 2002. Web. 01 Mar 2021.
Vancouver:
Ho M. Sequence variation and
covariation in forkhead domains. [Internet] [Thesis]. University of Hong Kong; 2002. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/10722/28162.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ho M. Sequence variation and
covariation in forkhead domains. [Thesis]. University of Hong Kong; 2002. Available from: http://hdl.handle.net/10722/28162
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Kansas State University
22.
Khosla, Aashima.
Regulatory
role of the START lipid/sterol binding domain in homeodomain
transcription factors from plants.
Degree: PhD, Biochemistry and Molecular
Biophysics Interdepartmental Program, 2015, Kansas State University
URL: http://hdl.handle.net/2097/35778
► Class IV homeodomain leucine-zipper transcription factors (HD-Zip TFs) are master regulators of cell-type differentiation in the plant epidermis. These transcription factors contain a putative START…
(more)
▼ Class IV homeodomain leucine-zipper
transcription
factors (HD-Zip TFs) are master regulators of cell-type
differentiation in the plant epidermis. These
transcription factors
contain a putative START (STeroidogenic Acute Regulatory
(StAR)-related lipid Transfer) lipid/sterolbinding domain that is
hypothesized to link metabolism to gene expression in plant
development. This study is focused on two class IV family members
that serve as models in many of the experiments: GLABRA2 (GL2) is a
key regulator of differentiation in hair cells called trichomes as
well as other epidermal cell types in various plant tissues. The
second member addressed in this study is PROTODERMAL FACTOR2
(PDF2), which plays a crucial role in epidermal cell specification
in shoots. A leading hypothesis is that the START domain, by
binding a ligand, controls
transcription factor function,
analogously to nuclear receptors from mammals. Domain swap
experiments indicated that the START domain from both plants and
mammals is a conserved ligand-binding motif that is required for
transcription factor activity. To further address its function in
ligand binding, mutational analysis of the START domain of GL2 was
performed. Several of the mutations remove charged residues in the
predicted ligand-binding pocket and resulted in loss-of-function
phenotypes, suggesting that ligand binding is critical for HD-Zip
TF activity. Chromatin immunoprecipitation–based sequencing
(ChIP-seq) revealed that the START domain is dispensable for
transcription factor binding to DNA. Using a high throughput
thermal shift assay to screen a library of pure natural compounds,
specific secondary metabolites were identified as putative START
domain ligands for PDF2. Experiments in both yeast and N.
benthamiana demonstrated that the START domain is required for
homodimerization of GL2 through its Zip domain. It was also found
that the START domains physically interact with RHAMNOSE SYNTHASE I
(RHM1). Further, this work provided evidence for a previously
elusive redundancy between GL2 and another class IV HD-Zip TF, and
unveils a positive feedback loop in the maintenance of the GL2
activity during trichome differentiation. Taken together, these
findings support the premise that START domains are central players
in metabolic regulatory networks that can modulate
transcription
factor activity by binding ligands and mediating protein-protein
interactions.
Advisors/Committee Members: Kathrin Schrick.
Subjects/Keywords: Lipids;
Transcription factors;
Arabidopsis
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Khosla, A. (2015). Regulatory
role of the START lipid/sterol binding domain in homeodomain
transcription factors from plants. (Doctoral Dissertation). Kansas State University. Retrieved from http://hdl.handle.net/2097/35778
Chicago Manual of Style (16th Edition):
Khosla, Aashima. “Regulatory
role of the START lipid/sterol binding domain in homeodomain
transcription factors from plants.” 2015. Doctoral Dissertation, Kansas State University. Accessed March 01, 2021.
http://hdl.handle.net/2097/35778.
MLA Handbook (7th Edition):
Khosla, Aashima. “Regulatory
role of the START lipid/sterol binding domain in homeodomain
transcription factors from plants.” 2015. Web. 01 Mar 2021.
Vancouver:
Khosla A. Regulatory
role of the START lipid/sterol binding domain in homeodomain
transcription factors from plants. [Internet] [Doctoral dissertation]. Kansas State University; 2015. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/2097/35778.
Council of Science Editors:
Khosla A. Regulatory
role of the START lipid/sterol binding domain in homeodomain
transcription factors from plants. [Doctoral Dissertation]. Kansas State University; 2015. Available from: http://hdl.handle.net/2097/35778

Massey University
23.
Cartwright, Gemma Maree.
Redox regulation of an AP-1-like transcription factor, YapA, in the fungal symbiont Epichloë festucae.
Degree: PhD, Genetics, 2013, Massey University
URL: http://hdl.handle.net/10179/4654
► Reactive oxygen species (ROS) are emerging as important regulators required for the successful establishment and maintenance of the mutualistic association between the fungal endophyte Epichloë…
(more)
▼ Reactive oxygen species (ROS) are emerging as important regulators required for
the successful establishment and maintenance of the mutualistic association between
the fungal endophyte Epichloë festucae and its grass host Lolium perenne (perennial
ryegrass). The generation of reactive oxygen species (ROS) by the fungal NADPH
oxidase, NoxA, has previously been shown to regulate hyphal growth of E. festucae in
planta, a result that has led to the hypothesis that fungal-produced ROS are key second
messengers in the symbiosis. However, the highly reactive nature of these molecules
dictates that cells possess efficient redox sensing mechanisms to maintain ROS
homeostasis and prevent oxidative damage to cellular components such as DNA,
lipids and proteins. The Saccharomyces cerevisiae Gpx3-Yap1 and Schizosaccharomyces
pombe Tpx1-Pap1, two-component H2O2 sensors, serve as model redox relays for
coordinating the cellular response to ROS. While proteins related to the Yap1 and Pap1
basic-leucine zipper (bZIP) transcription factors have been identified in a number of
filamentous fungi, the components involved in the upstream regulation remain
unclear. This thesis presents an investigation into the role of the E. festucae Yap1
homologue, YapA, and putative upstream activators GpxC and TpxA, homologues of
Gpx3 and Tpx1, respectively, in responding to ROS. YapA is involved in responding to
ROS generated at the wound site following inoculation into ryegrass seedlings.
However, deletion of yapA did not impair fungal colonisation of the host, indicating
functional redundancy in systems used by E. festucae to sense and respond to plantproduced
ROS. In culture, deletion of E. festucae yapA renders the mutants sensitive to
only a subset of ROS and this sensitivity is influenced by the stage of fungal
development. In contrast to the H2O2-sensitive phenotype widely reported for fungi
lacking the Yap1-like protein, the E. festucae yapA mutant maintains wild-type mycelial
resistance to H2O2 but conidia of the yapA mutant are sensitive to H2O2. Using a
degron-tagged GFP-CL1 as a reporter, we found YapA is required for the expression of
the spore-specific catalase, catA. Moreover, YapA is activated by H2O2, through
disulfide bond formation, independently of both GpxC and TpxA, suggesting a novel
mechanism of regulation exists in E. festucae. This work provides a comprehensive
analysis of the role and regulation of the AP-1 transcription factor pathway in a
filamentous fungal species.
Subjects/Keywords: Epichloë;
Genetics;
Transcription factors
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cartwright, G. M. (2013). Redox regulation of an AP-1-like transcription factor, YapA, in the fungal symbiont Epichloë festucae. (Doctoral Dissertation). Massey University. Retrieved from http://hdl.handle.net/10179/4654
Chicago Manual of Style (16th Edition):
Cartwright, Gemma Maree. “Redox regulation of an AP-1-like transcription factor, YapA, in the fungal symbiont Epichloë festucae.” 2013. Doctoral Dissertation, Massey University. Accessed March 01, 2021.
http://hdl.handle.net/10179/4654.
MLA Handbook (7th Edition):
Cartwright, Gemma Maree. “Redox regulation of an AP-1-like transcription factor, YapA, in the fungal symbiont Epichloë festucae.” 2013. Web. 01 Mar 2021.
Vancouver:
Cartwright GM. Redox regulation of an AP-1-like transcription factor, YapA, in the fungal symbiont Epichloë festucae. [Internet] [Doctoral dissertation]. Massey University; 2013. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/10179/4654.
Council of Science Editors:
Cartwright GM. Redox regulation of an AP-1-like transcription factor, YapA, in the fungal symbiont Epichloë festucae. [Doctoral Dissertation]. Massey University; 2013. Available from: http://hdl.handle.net/10179/4654

Michigan State University
24.
Bilgin, Betul.
Parallel, quantitative analysis of transcription factors.
Degree: 2014, Michigan State University
URL: http://etd.lib.msu.edu/islandora/object/etd:2691
► Thesis Ph. D. Michigan State University. Chemical Engineering 2014.
Cellular and tissue homeostasis is a result of complex processes that respond to the cellular microenvironment.…
(more)
▼ Thesis Ph. D. Michigan State University. Chemical Engineering 2014.
Cellular and tissue homeostasis is a result of complex processes that respond to the cellular microenvironment. To understand these processes and the signaling thatinitiates them, it is important to measure the levels of many cellular components. Continuing technology development, especially in high-throughput and parallel techniques, will provide new assays for such measurements. If designed well, these techniques can also be applied in the clinical setting, with the potential to improve human health through improved disease detection and diagnosis. Currently, the majorityof these techniques measure the results of cellular signaling, e.g., changes in mRNA levels. It would provide complementary information to measure the levels and activities of transcription factors, the upstream mediators of cell signaling. Transcription factors (TFs) are proteins that alter the expression of target genes in response to stimuli. They bind specific sites on chromosomal DNA, resulting in activation or repression of nearby genes. Many TFs respond to a variety of signals, and multiple TF levels can be altered by a single stimulus. Moreover, TF levels are dynamic, in general, changing with time in concert with changes in the cell phenotype and the microenvironment. As there are ~2000 TFs in humans and their levels change dynamically, measuring TF levels and activities in parallel is a challenging task.To address this challenge, techniques have been developed to measure TF levels in parallel. While these assays have provided valuable information on cellular processes, each has limitations. The aim of this dissertation was to develop a parallel, quantitative TF measurement method that leverages established DNA analytical technologies and would complement existing analytical approaches. This work focused on technology development and the application of the assay to poorly-characterized biological processes. The initial focus was on assay development. The assay was based on magnetic bead separation of TF-bound DNA probes. We measured purified TFs, p50 (NF-kB family) and c-Jun (AP-1 family), in parallel with ~10-fold improved sensitivity over existing approaches. TF levels were successfully measured in nuclear extracts from breast cancer cells. The results agreed with the previously published data, showing that the assay achieved successful parallel and quantitative detection of TFs. To further demonstrate the applicability of the approach, temporal measurements of TF levels were performed in different cell types and in response to different stimuli. TNF-a treated HepG2 cells and breast cancer cells were selected as model systems. Levels of TFs, NF-kB, Stat3, CREB, GR and TBP, were dynamically measured in these nuclear extracts. Furthermore, the same set of TF levels were measured in untreated and palmitic acid treated HepG2 cells. The observed changes in these TF levels have furthered our understanding of the molecular mechanisms associated with cellular exposure to…
Advisors/Committee Members: Walton, S. Patrick, Worden, Robert, Chan, Christina, Koslowsky, Donna.
Subjects/Keywords: Transcription factors – Analysis; Chemical engineering
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bilgin, B. (2014). Parallel, quantitative analysis of transcription factors. (Thesis). Michigan State University. Retrieved from http://etd.lib.msu.edu/islandora/object/etd:2691
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):
Bilgin, Betul. “Parallel, quantitative analysis of transcription factors.” 2014. Thesis, Michigan State University. Accessed March 01, 2021.
http://etd.lib.msu.edu/islandora/object/etd:2691.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Bilgin, Betul. “Parallel, quantitative analysis of transcription factors.” 2014. Web. 01 Mar 2021.
Vancouver:
Bilgin B. Parallel, quantitative analysis of transcription factors. [Internet] [Thesis]. Michigan State University; 2014. [cited 2021 Mar 01].
Available from: http://etd.lib.msu.edu/islandora/object/etd:2691.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Bilgin B. Parallel, quantitative analysis of transcription factors. [Thesis]. Michigan State University; 2014. Available from: http://etd.lib.msu.edu/islandora/object/etd:2691
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
25.
NC DOCKS at The University of North Carolina at Greensboro; Vervaecke, Lauren Suzanne.
Acute and chronic exercise effects on NrF2 and antioxidants in the muscle and brain tissue of Sprague Dawley rats.
Degree: 2017, NC Docks
URL: http://libres.uncg.edu/ir/uncg/f/Vervaecke_uncg_0154D_12387.pdf
► Nuclear factor erythroid 2 related factor 2 (NrF2), is an essential transcription factor and a master regulator of the antioxidant defense system, which increases antioxidants…
(more)
▼ Nuclear factor erythroid 2 related factor 2 (NrF2), is an essential transcription factor and a master regulator of the antioxidant defense system, which increases antioxidants in response to the production of reactive oxygen and nitrogen species (RONS). Disproportional increases in RONS compared to antioxidant defense capabilities can induce a state of oxidative stress (OS). Aerobic exercise of sufficient intensity and duration is well-known to increase the production of RONS in the blood, skeletal muscle and brain. Chronic aerobic exercise has been shown to mediate OS through increases in antioxidant factors. However, there are only two studies that have reported changes in NrF2 in response to aerobic exercise in a healthy cohort, but were limited to chronic exercise and examined the striatum brain region and whole brain only. The purpose of this study was to 1) determine the extent to which markers of OS (MDA, GSSG, GSSG/TGSH) change with acute aerobic exercise in the blood, skeletal muscle and brain, 2) determine the extent to which antioxidant defense factors (GSH, TGSH, Mn-SOD) change with chronic aerobic exercise in skeletal muscle and brain, and 3) determine the extent to which NrF2 protein concentration changes with acute and chronic aerobic exercise in skeletal muscle and specific brain regions (cerebral cortex, hippocampus, and cerebellum). To accomplish these objectives, three groups of rats (n=6-13/group), sedentary (SD), acute exercise (AE) and chronic exercise (ET) (5-7 weeks), ran at an intensity equal to 75% VO2max or served as controls. Gastrocnemius skeletal muscle and cerebral cortex, hippocampus, and cerebellum brain regions were analyzed using multiple methods to examine markers of OS, antioxidant factors and NrF2 protein concentration. AE significantly increased MDA concentration in the blood (~69%) and the hippocampus brain region (~36%). However, the OS response did not reflect a significant increase in NrF2 protein concentration with AE in the brain or skeletal muscle. In fact, NrF2 was significantly reduced in all brain regions and muscle with AE compared to SD. ET significantly increased GSH (~27%) and TGSH (~26%) in the hippocampus brain regions, which was concomitant with a significant increase in NrF2 protein concentration in the hippocampus with ET. In contrast, GSH, TGSH, and Mn-SOD (~44%) were significantly reduced in the in gastrocnemius skeletal muscle with ET. There were no significant differences in antioxidant factors in the cortex or cerebellum brain regions, which coincided with the lack of significant elevation in NrF2 with training. In summary, these data suggest that ET for 5-7 weeks at 75% VO2max was sufficient to increase NrF2 protein concentration and antioxidant factors in the hippocampus, a brain region that is highly susceptible to neurodegeneration. However, the single bout of acute aerobic exercise appears to be inadequate to sufficiently stress the brain and skeletal muscle tissue to increase markers of OS or NrF2 protein concentration.
Subjects/Keywords: Antioxidants; Aerobic exercises; Transcription factors
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
NC DOCKS at The University of North Carolina at Greensboro; Vervaecke, L. S. (2017). Acute and chronic exercise effects on NrF2 and antioxidants in the muscle and brain tissue of Sprague Dawley rats. (Thesis). NC Docks. Retrieved from http://libres.uncg.edu/ir/uncg/f/Vervaecke_uncg_0154D_12387.pdf
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):
NC DOCKS at The University of North Carolina at Greensboro; Vervaecke, Lauren Suzanne. “Acute and chronic exercise effects on NrF2 and antioxidants in the muscle and brain tissue of Sprague Dawley rats.” 2017. Thesis, NC Docks. Accessed March 01, 2021.
http://libres.uncg.edu/ir/uncg/f/Vervaecke_uncg_0154D_12387.pdf.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
NC DOCKS at The University of North Carolina at Greensboro; Vervaecke, Lauren Suzanne. “Acute and chronic exercise effects on NrF2 and antioxidants in the muscle and brain tissue of Sprague Dawley rats.” 2017. Web. 01 Mar 2021.
Vancouver:
NC DOCKS at The University of North Carolina at Greensboro; Vervaecke LS. Acute and chronic exercise effects on NrF2 and antioxidants in the muscle and brain tissue of Sprague Dawley rats. [Internet] [Thesis]. NC Docks; 2017. [cited 2021 Mar 01].
Available from: http://libres.uncg.edu/ir/uncg/f/Vervaecke_uncg_0154D_12387.pdf.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
NC DOCKS at The University of North Carolina at Greensboro; Vervaecke LS. Acute and chronic exercise effects on NrF2 and antioxidants in the muscle and brain tissue of Sprague Dawley rats. [Thesis]. NC Docks; 2017. Available from: http://libres.uncg.edu/ir/uncg/f/Vervaecke_uncg_0154D_12387.pdf
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Rutgers University
26.
Patel, Sahishnu V., 1988-.
NanoScript: a nanoparticle-based biomimetic platform for stem cell reprogramming.
Degree: PhD, Chemistry and Chemical Biology, 2015, Rutgers University
URL: https://rucore.libraries.rutgers.edu/rutgers-lib/48620/
► Stem cell engineering for regenerative medicine offers new hope for treating many ailments and injuries. Hence, there is an urgent demand by stem cell scientists…
(more)
▼ Stem cell engineering for regenerative medicine offers new hope for treating many ailments and injuries. Hence, there is an urgent demand by stem cell scientists for an alternative platform that induces stem cell differentiation in a safe and efficient manner. Stem cell differentiation is inherently regulated by transcription factors (TFs), which are multi-domain proteins that interact with DNA to control expression of target genes, and thus, TFs are master regulators of gene expression and cellular behavior. Recently, scientists have developed synthetic transcription factors (STFs), which are small molecules that mimic the function of the individual domains on TF proteins. This work presents the development a novel bio-inspired platform called NanoScript, which is an alternative approach for safe stem cell differentiation. NanoScript is a nanoparticle-based artificial TF protein because it is designed to replicate the function and structure of natural TF proteins. NanoScript was constructed by assembling STFs onto multifunctional nanoparticles. We first demonstrate that NanoScript localizes within the nucleus of cells, initiates transcription of a reporter plasmid by over 15-fold in cancer cells, and transcribes endogenous genes. The tunable and interchangeable components of NanoScript can easily be modified to either activate or deactivate any gene of interest. As a result, NanoScript was then demonstrated for three stem cell-based applications: 1) NanoScript targets myogenic genes to differentiate adipose-derived mesenchymal stem cells (ADMSCs) into muscle cells, 2) NanoScript modified with an epigenetic modulator, CTB, increases transcriptional potency and enhances differentiation of ADMACs into chondrocytes, and 3) NanoScript redesigned with gene repression molecules acts a transcriptional repressor protein because it downregulates gene expression to induce differentiation of neural stem cells into functional neurons. Because of its robust tunability and biocompatibility, the patented NanoScript platform is a promising alternative tool for research scientists for applications involving gene manipulation such as stem cell differentiation, cancer therapy, and cellular reprogramming. Moreover, the ability of NanoScript to induce stem cell differentiation in a non-viral and footprint-free manner is highly desired by stem cell clinicians, and hence, holds potential for use in stem cell-based therapies.
Advisors/Committee Members: Lee, KiBum (chair), Brennan, John (internal member), Li, Jing (internal member), Kwan, Kelvin (outside member).
Subjects/Keywords: Nanoparticles; Stem cells; Transcription factors
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Patel, Sahishnu V., 1. (2015). NanoScript: a nanoparticle-based biomimetic platform for stem cell reprogramming. (Doctoral Dissertation). Rutgers University. Retrieved from https://rucore.libraries.rutgers.edu/rutgers-lib/48620/
Chicago Manual of Style (16th Edition):
Patel, Sahishnu V., 1988-. “NanoScript: a nanoparticle-based biomimetic platform for stem cell reprogramming.” 2015. Doctoral Dissertation, Rutgers University. Accessed March 01, 2021.
https://rucore.libraries.rutgers.edu/rutgers-lib/48620/.
MLA Handbook (7th Edition):
Patel, Sahishnu V., 1988-. “NanoScript: a nanoparticle-based biomimetic platform for stem cell reprogramming.” 2015. Web. 01 Mar 2021.
Vancouver:
Patel, Sahishnu V. 1. NanoScript: a nanoparticle-based biomimetic platform for stem cell reprogramming. [Internet] [Doctoral dissertation]. Rutgers University; 2015. [cited 2021 Mar 01].
Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/48620/.
Council of Science Editors:
Patel, Sahishnu V. 1. NanoScript: a nanoparticle-based biomimetic platform for stem cell reprogramming. [Doctoral Dissertation]. Rutgers University; 2015. Available from: https://rucore.libraries.rutgers.edu/rutgers-lib/48620/

University of Texas Southwestern Medical Center
27.
Dambach, Michael David.
Defining the Constellation of RNA Elements That Associate with Bacillus Subtilis HFQ.
Degree: 2013, University of Texas Southwestern Medical Center
URL: http://hdl.handle.net/2152.5/1240
► Bacteria utilize a wide variety of genetic regulatory strategies in order to sense and respond to various environmental fluctuations in nutrient availability, temperature, salinity, and…
(more)
▼ Bacteria utilize a wide variety of genetic regulatory strategies in order to sense and respond to various environmental fluctuations in nutrient availability, temperature, salinity, and oxygen among others. As such, bacterial species have evolved highly coordinated and tightly regulated systems as a means of efficiently responding to potentially deleterious changes in environmental conditions. Traditionally DNA binding transcriptions
factors were thought to be the primary means by which the cell executes a selective genetic response. However, the advent of microarray and next generation sequencing platforms, coupled with the wealth of sequenced genomes and powerful bioinformatics have revealed that RNA mediated post transcriptional gene regulation is wide spread in bacterial species and may in fact rival protein based regulatory systems in scope and breadth.
RNA mediated post transcriptional gene regulation is broadly divided into two categories-those in which the RNA element is transcribed with the mRNA it regulates (cis-acting regulatory RNAs) or those which are transcribed independently from the gene that they regulate (trans-acting regulatory RNAs). In general cis-acting RNA elements are embedded within a 5' UTR of a gene that they regulate and may or may not require a protein cofactor to execute genetic regulation. Whereas, trans-acting regulatory RNAs, also known as sRNAs, function via base pairing with their target mRNA and this usually requires the protein chaperone Hfq. Hfq mediated gene regulation is poorly understood in Gram-positive organism, thus I undertook studies of this protein in the model Gram-positive organism Bacillus subtilis. I used co-immunoprecipitation and deep-sequencing to define the suite of RNA elements that associate with this regulatory protein. In addition I performed global transcriptomic studies on an Hfq deletion mutant in order to identify genes that are regulated via Hfq. These studies identified sRNAs that may be involved with sporulation. This led me to analyze the transcriptomic profile of Bacillus subtilis spores in an attempt to identify new sRNA regulators.
Advisors/Committee Members: Winkler, Wade C..
Subjects/Keywords: Bacillus subtilis; Integration Host Factors; Transcription Factors
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Dambach, M. D. (2013). Defining the Constellation of RNA Elements That Associate with Bacillus Subtilis HFQ. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1240
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):
Dambach, Michael David. “Defining the Constellation of RNA Elements That Associate with Bacillus Subtilis HFQ.” 2013. Thesis, University of Texas Southwestern Medical Center. Accessed March 01, 2021.
http://hdl.handle.net/2152.5/1240.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Dambach, Michael David. “Defining the Constellation of RNA Elements That Associate with Bacillus Subtilis HFQ.” 2013. Web. 01 Mar 2021.
Vancouver:
Dambach MD. Defining the Constellation of RNA Elements That Associate with Bacillus Subtilis HFQ. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2013. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/2152.5/1240.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Dambach MD. Defining the Constellation of RNA Elements That Associate with Bacillus Subtilis HFQ. [Thesis]. University of Texas Southwestern Medical Center; 2013. Available from: http://hdl.handle.net/2152.5/1240
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Ryerson University
28.
Shawaf, Zainab Al.
The characterization of MCEF : an AFF transcription factor associated with acute lymphoglastic leukemia and HIV-1.
Degree: 2010, Ryerson University
URL: https://digital.library.ryerson.ca/islandora/object/RULA%3A6301
► Acute Lymphoblastic Leukemia (ALL) results from environmentally-triggered in utero translocations between the Mixed Lineage Leukemia (MLL) gene and partner genes. In the most frequent cases…
(more)
▼ Acute Lymphoblastic Leukemia (ALL) results from environmentally-triggered in utero translocations between the Mixed Lineage Leukemia (MLL) gene and partner genes. In the most frequent cases of ALL, this partner gene is one of the AF4 family (AFF) of transcription factors. The newest AFF member to be discovered and cloned is AFF-4/AF5q31/MCEF. MCEF interacts with a transcription factor necessary for transcription of HIV-1. In addition, evidence suggests that male knockout mice are azoospermic. Therefore, the characterization of MCEF is clinically and theoretically important. The purpose of my research was to further characterize MCEF. In this paper, I first review the AFF members, focusing on MCEF. I then show a series of experimental results addressing MCEF isoforms and HIV-1 repression domains, as well as the generation of anti-MCEF antisera. Finally, I highlight intriguing results with live virus replication assays that suggest how MCEF could be exploited as a therapeutic target for AIDS.
Subjects/Keywords: Lymphoblastic leukemia; Transcription factors; Transcription factors – Research – Methodology
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Shawaf, Z. A. (2010). The characterization of MCEF : an AFF transcription factor associated with acute lymphoglastic leukemia and HIV-1. (Thesis). Ryerson University. Retrieved from https://digital.library.ryerson.ca/islandora/object/RULA%3A6301
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):
Shawaf, Zainab Al. “The characterization of MCEF : an AFF transcription factor associated with acute lymphoglastic leukemia and HIV-1.” 2010. Thesis, Ryerson University. Accessed March 01, 2021.
https://digital.library.ryerson.ca/islandora/object/RULA%3A6301.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Shawaf, Zainab Al. “The characterization of MCEF : an AFF transcription factor associated with acute lymphoglastic leukemia and HIV-1.” 2010. Web. 01 Mar 2021.
Vancouver:
Shawaf ZA. The characterization of MCEF : an AFF transcription factor associated with acute lymphoglastic leukemia and HIV-1. [Internet] [Thesis]. Ryerson University; 2010. [cited 2021 Mar 01].
Available from: https://digital.library.ryerson.ca/islandora/object/RULA%3A6301.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Shawaf ZA. The characterization of MCEF : an AFF transcription factor associated with acute lymphoglastic leukemia and HIV-1. [Thesis]. Ryerson University; 2010. Available from: https://digital.library.ryerson.ca/islandora/object/RULA%3A6301
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – San Diego
29.
Tsunemoto, Rachel.
Deciphering Transcriptional Control of Neuronal Identity and Diversity Using Direct Reprogramming.
Degree: Neurosciences, 2016, University of California – San Diego
URL: http://www.escholarship.org/uc/item/59k3t2xt
► The mammalian nervous system is comprised of an unknown, but recognizably large, number of diverse neuronal subtypes. Recently, direct reprogramming (also known as transdifferentiation) has…
(more)
▼ The mammalian nervous system is comprised of an unknown, but recognizably large, number of diverse neuronal subtypes. Recently, direct reprogramming (also known as transdifferentiation) has become an established method to rapidly produce “induced” neurons of numerous different subtypes directly from fibroblasts by overexpressing specific combinations of transcription factors and/or microRNAs. This technique not only provides the means to study various neuronal subtype populations that are not easily accessible, particularly in humans, but it also serves as a tool to interrogate the transcriptional codes that regulate neuronal subtype identity and maintenance. Both in vivo studies and direct reprogramming protocols have demonstrated that basic helix-loop-helix (bHLH) and Pit-Oct-Unc (POU) transcription factors can aid in the specification of distinct neuronal subtypes. Therefore, we set out to comprehensively and systematically address whether first, additional bHLH and POU factor pairings could reprogram fibroblasts into functional neurons and second, dissect out the discrete and synergistic roles of these factors in neuronal subtype specification. We discovered over 70 novel pairs of bHLH and POU (and non-POU) transcription factors sufficient to generate candidate induced neurons (iNs) from mouse embryonic fibroblasts. Transcriptomic analysis of 35 of these candidate iN populations revealed gene expression profiles similar to those of endogenous neuronal populations. Additionally, differences between iN populations were observed at both a transcriptional and functional level.
Subjects/Keywords: Neurosciences; Direct Reprogramming; Induced Neurons; Transcription Factors
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Tsunemoto, R. (2016). Deciphering Transcriptional Control of Neuronal Identity and Diversity Using Direct Reprogramming. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/59k3t2xt
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):
Tsunemoto, Rachel. “Deciphering Transcriptional Control of Neuronal Identity and Diversity Using Direct Reprogramming.” 2016. Thesis, University of California – San Diego. Accessed March 01, 2021.
http://www.escholarship.org/uc/item/59k3t2xt.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Tsunemoto, Rachel. “Deciphering Transcriptional Control of Neuronal Identity and Diversity Using Direct Reprogramming.” 2016. Web. 01 Mar 2021.
Vancouver:
Tsunemoto R. Deciphering Transcriptional Control of Neuronal Identity and Diversity Using Direct Reprogramming. [Internet] [Thesis]. University of California – San Diego; 2016. [cited 2021 Mar 01].
Available from: http://www.escholarship.org/uc/item/59k3t2xt.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Tsunemoto R. Deciphering Transcriptional Control of Neuronal Identity and Diversity Using Direct Reprogramming. [Thesis]. University of California – San Diego; 2016. Available from: http://www.escholarship.org/uc/item/59k3t2xt
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Hong Kong
30.
陳志平.
Requirement of N-linked
glycosylation for optimal proteolytic activation of liver-enriched
transcription factor CREB-H.
Degree: 2010, University of Hong Kong
URL: http://hdl.handle.net/10722/131808
Subjects/Keywords: Glycosylation.;
Transcription factors.
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
陳志平. (2010). Requirement of N-linked
glycosylation for optimal proteolytic activation of liver-enriched
transcription factor CREB-H. (Thesis). University of Hong Kong. Retrieved from http://hdl.handle.net/10722/131808
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
陳志平. “Requirement of N-linked
glycosylation for optimal proteolytic activation of liver-enriched
transcription factor CREB-H.” 2010. Thesis, University of Hong Kong. Accessed March 01, 2021.
http://hdl.handle.net/10722/131808.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
陳志平. “Requirement of N-linked
glycosylation for optimal proteolytic activation of liver-enriched
transcription factor CREB-H.” 2010. Web. 01 Mar 2021.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Vancouver:
陳志平. Requirement of N-linked
glycosylation for optimal proteolytic activation of liver-enriched
transcription factor CREB-H. [Internet] [Thesis]. University of Hong Kong; 2010. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/10722/131808.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
陳志平. Requirement of N-linked
glycosylation for optimal proteolytic activation of liver-enriched
transcription factor CREB-H. [Thesis]. University of Hong Kong; 2010. Available from: http://hdl.handle.net/10722/131808
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Not specified: Masters Thesis or Doctoral Dissertation
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