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Vanderbilt University
1.
Benton, Mary Lauren.
Genome-wide Enhancer Maps Differ Significantly in their Genomic Distribution, Evolution, and Function.
Degree: MS, Biomedical Informatics, 2018, Vanderbilt University
URL: http://hdl.handle.net/1803/13969
► Non-coding gene regulatory enhancers are essential to transcription in mammalian cells. As a result, a large variety of experimental and computational strategies have been developed…
(more)
▼ Non-coding
gene regulatory enhancers are essential to transcription in mammalian cells. As a result, a large variety of experimental and computational strategies have been developed to identify cis-regulatory enhancer sequences. In practice, most studies consider enhancers identified by only a single method, and the concordance of enhancers identified by different methods has not been comprehensively evaluated. We assessed the similarities of enhancer sets identified by representative strategies in four biological contexts and evaluated the robustness of downstream conclusions to the choice of identification strategy. We demonstrate significant dissimilarity between enhancer sets in their genomic characteristics, evolutionary conservation, and association with functional loci within each context. The disagreement is sufficient to influence interpretation of GWAS SNPs and eQTL, and to lead to disparate conclusions about enhancer biology and disease mechanisms. We also find only limited evidence that regions identified by multiple enhancer identification methods are better candidates than those identified by a single method. As a result, we cannot recommend the use of any enhancer identification strategy in isolation. While these findings highlight a major challenge to mapping the genetic architecture of complex disease and interpreting regulatory variants found in patient genomes, a systematic understanding of similarities and differences in enhancer identification methodology will ultimately enable robust inferences about
gene regulatory sequences.
Advisors/Committee Members: Emily Hodges (committee member), Jacob J Hughey (committee member), John A Capra (Committee Chair).
Subjects/Keywords: gene regulation
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APA (6th Edition):
Benton, M. L. (2018). Genome-wide Enhancer Maps Differ Significantly in their Genomic Distribution, Evolution, and Function. (Thesis). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/13969
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):
Benton, Mary Lauren. “Genome-wide Enhancer Maps Differ Significantly in their Genomic Distribution, Evolution, and Function.” 2018. Thesis, Vanderbilt University. Accessed March 01, 2021.
http://hdl.handle.net/1803/13969.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Benton, Mary Lauren. “Genome-wide Enhancer Maps Differ Significantly in their Genomic Distribution, Evolution, and Function.” 2018. Web. 01 Mar 2021.
Vancouver:
Benton ML. Genome-wide Enhancer Maps Differ Significantly in their Genomic Distribution, Evolution, and Function. [Internet] [Thesis]. Vanderbilt University; 2018. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/1803/13969.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Benton ML. Genome-wide Enhancer Maps Differ Significantly in their Genomic Distribution, Evolution, and Function. [Thesis]. Vanderbilt University; 2018. Available from: http://hdl.handle.net/1803/13969
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Vanderbilt University
2.
Broeckelmann, Eva Marie.
Dynamics of long-range gene regulation at the BMP2 locus.
Degree: MS, Interdisciplinary Studies: Human Genetics, 2013, Vanderbilt University
URL: http://hdl.handle.net/1803/12090
► A member of the TGF-â superfamily of cytokines, BMP2 not only plays a critical role in pattern formation and morphogenesis during early embryonic development, but…
(more)
▼ A member of the TGF-â superfamily of cytokines, BMP2 not only plays a critical role in pattern formation and morphogenesis during early embryonic development, but also promotes osteoblast differentiation and bone formation, making it a vital factor for the maintenance of bone health. Expanding on earlier studies of the regulatory landscape surrounding Bmp2 by BAC transgenesis in mice that had lead to the identification of the osteoblast enhancer ECR1, the work presented here further scrutinizes the particular role of ECR1 during osteogenesis and provides striking evidence for the hypothesis that – despite its indispensable role for Bmp2 expression in osteoblasts -, it is in fact not entirely autonomous, but requires additional enhancer activity to control the full scope of osteoblast-specific expression. Subsequent analysis of the chromosomal conformation during transcriptional activation does not only support this hypothesis and substantiate the dynamic nature of looping interactions at the locus, but combined with additional epigenetic characteristics also serves to highlight several distant loci within the
gene desert as excellent candidates for putative enhancer function.
Advisors/Committee Members: Xiangli Yang (committee member), Michelle Southard-Smith (committee member), Douglas P. Mortlock (Committee Chair).
Subjects/Keywords: gene regulation; Bmp2
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Broeckelmann, E. M. (2013). Dynamics of long-range gene regulation at the BMP2 locus. (Thesis). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/12090
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):
Broeckelmann, Eva Marie. “Dynamics of long-range gene regulation at the BMP2 locus.” 2013. Thesis, Vanderbilt University. Accessed March 01, 2021.
http://hdl.handle.net/1803/12090.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Broeckelmann, Eva Marie. “Dynamics of long-range gene regulation at the BMP2 locus.” 2013. Web. 01 Mar 2021.
Vancouver:
Broeckelmann EM. Dynamics of long-range gene regulation at the BMP2 locus. [Internet] [Thesis]. Vanderbilt University; 2013. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/1803/12090.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Broeckelmann EM. Dynamics of long-range gene regulation at the BMP2 locus. [Thesis]. Vanderbilt University; 2013. Available from: http://hdl.handle.net/1803/12090
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
3.
Morrissey, Chris S.
Understanding the epigenetics of erythroid differentiation through the power of deep sequencing
.
Degree: 2013, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/19905
► Next generation sequencing, or high throughput sequencing, is just over a decade old. In that time the technologies have changed so rapidly that sequencing has…
(more)
▼ Next generation sequencing, or high throughput sequencing, is just over a decade old. In that time the technologies have changed so rapidly that sequencing has been surpassing Moore’s Law in that sequencing capacity has been doubling in less than the 18 month pace at which computing power has been doubling since the late 1950s. This prodigious increase in the ability to sequence DNA fragments coupled with the precipitous drop in price has lead to an explosion of the number and type of biological experiments possible. In the ten years since the mouse genome was first sequenced we have gone from being able to detect sequence feature like open reading frames, to being able to compare multiple species revealing differing patterns of evolutionary constraint, to being able to determine the genomic distribution of a whole host of epigenetic features such as histone modifications and DNA bound transcription factors, to being able to sequence cDNA reflections of transcripts.
In this dissertation I lay out a strategy for efficiently analyzing and interpreting the mountains of data resulting from modern sequencing experiments. I discuss the software tools used to process sequencing data, and touch on the important runtime parameters. I provide uniform analysis workflows for transcription factor and histone modification ChIP-seq experiments which I have personally used to process data from 55 sequencing experiments. I go on to discuss some of the potential pitfalls that should be avoided, and I provide a blacklist that can be used to filter artifacts from ChIP-seq results.
When a transcription factor ChIP-seq experiment is performed, the desired product is a list of genomic locations bound by the transcription factor of interest. To obtain this list, we turn to peak-calling software that interprets the pileup of sequencing reads to determine peak locations. Unfortunately the resulting peaks are very dependent on the peak-calling threshold and other parameters not all of which are well understood. I explore the inherent reproducibility of peak calling in ChIP-seq experiments, and through a combination of sub-sampling and vote counting strive to improve our understanding of peak quality and reproducibility.
Finally, I integrate the fruits of my sequencing analysis to illuminate the epigenetics of erythroid differentiation. The Hardison lab utilizes the G1E(Weiss, Yu, & Orkin, 1997) cell line as a model of murine erythropoeisis. G1E cells are an erythroid committed Gata1 knockout cell line derived from mouse embryonic stem cells. GATA1 is a master regulator for erythropoeisis, and without it the G1E cells are stuck in a self renewing erythroid progenitor stage. G1E-ER4 is a GATA1 rescue subline of G1E in which GATA1 can be induced, and differentiation toward erythrocytes can be restored. This is a beautiful system for studying the cascade of differential processes set in motion by the action of this master regulator. Here I use DNase-seq to identify an unprecedentedly comprehensive set of regulatory genomic regions…
Advisors/Committee Members: Ross Cameron Hardison, Dissertation Advisor/Co-Advisor, Webb Colby Miller, Committee Chair/Co-Chair, Michael Axtell, Committee Member, Qunhua Li, Committee Member, David John Vandenbergh, Committee Member.
Subjects/Keywords: Epigenetic gene regulation
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Morrissey, C. S. (2013). Understanding the epigenetics of erythroid differentiation through the power of deep sequencing
. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/19905
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):
Morrissey, Chris S. “Understanding the epigenetics of erythroid differentiation through the power of deep sequencing
.” 2013. Thesis, Penn State University. Accessed March 01, 2021.
https://submit-etda.libraries.psu.edu/catalog/19905.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Morrissey, Chris S. “Understanding the epigenetics of erythroid differentiation through the power of deep sequencing
.” 2013. Web. 01 Mar 2021.
Vancouver:
Morrissey CS. Understanding the epigenetics of erythroid differentiation through the power of deep sequencing
. [Internet] [Thesis]. Penn State University; 2013. [cited 2021 Mar 01].
Available from: https://submit-etda.libraries.psu.edu/catalog/19905.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Morrissey CS. Understanding the epigenetics of erythroid differentiation through the power of deep sequencing
. [Thesis]. Penn State University; 2013. Available from: https://submit-etda.libraries.psu.edu/catalog/19905
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
4.
Fulco, Charles Perry.
Measuring and Predicting Enhancer-Promoter Communication.
Degree: PhD, 2019, Harvard University
URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029649
► Mammalian genomes harbor millions of noncoding elements called enhancers that quantitatively regulate gene expression, but it remains unclear which enhancers regulate which genes. A key…
(more)
▼ Mammalian genomes harbor millions of noncoding elements called enhancers that quantitatively regulate gene expression, but it remains unclear which enhancers regulate which genes. A key bottleneck in understanding the regulatory wiring that connects noncoding regulatory elements to specific target genes has been that we have lacked scalable experimental approaches for perturbing enhancers in the genome and determining their effects on gene expression. To address this challenge, we developed new experimental approaches to systematically quantify the effects of enhancers regulating a gene of interest in a given cell type. Applying these approaches to dozens of genes uncovered complex networks of regulatory connections that could not be predicted by any existing approach. Strikingly, a simple equation based on a mechanistic model for enhancer function performed remarkably well at predicting the complex patterns of regulatory connections we observed in our datasets. This Activity-by-Contact (ABC) model involves multiplying measures of enhancer activity and enhancer-promoter 3D contacts, and can predict enhancer-gene connections based on chromatin state maps. Together, these experimental and computational approaches provide a systematic framework to understand gene regulation by enhancers and will catalyze efforts to interpret human genetic variation and manipulate gene expression for therapeutic purposes.
Systems Biology
Advisors/Committee Members: Bulyk, Martha (advisor), Sharp, Phillip (committee member), Adelman, Karen (committee member).
Subjects/Keywords: Gene Regulation; CRISPR
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APA ·
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APA (6th Edition):
Fulco, C. P. (2019). Measuring and Predicting Enhancer-Promoter Communication. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029649
Chicago Manual of Style (16th Edition):
Fulco, Charles Perry. “Measuring and Predicting Enhancer-Promoter Communication.” 2019. Doctoral Dissertation, Harvard University. Accessed March 01, 2021.
http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029649.
MLA Handbook (7th Edition):
Fulco, Charles Perry. “Measuring and Predicting Enhancer-Promoter Communication.” 2019. Web. 01 Mar 2021.
Vancouver:
Fulco CP. Measuring and Predicting Enhancer-Promoter Communication. [Internet] [Doctoral dissertation]. Harvard University; 2019. [cited 2021 Mar 01].
Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029649.
Council of Science Editors:
Fulco CP. Measuring and Predicting Enhancer-Promoter Communication. [Doctoral Dissertation]. Harvard University; 2019. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029649

Rice University
5.
Narula, Jatin.
Design Principles of Cellular Differentiation Regulatory Networks.
Degree: PhD, Engineering, 2015, Rice University
URL: http://hdl.handle.net/1911/88375
► To understand cellular differentiation programs is to understand the often large and complex gene regulatory networks (GRNs) that control and orchestrate these programs. The work…
(more)
▼ To understand cellular differentiation programs is to understand the often large and complex
gene regulatory networks (GRNs) that control and orchestrate these programs. The work presented here aims to exploit the wealth of newly available experimental information and methods to identify design principles that relate how GRN structures relate to the functional requirements in three model differentiation/stress-response programs: embryonic hematopoiesis, sporulation and σB general stress response. First we used a statistical thermodynamic approach to characterize the biophysical mechanisms of combinatorial
regulation by distant enhancers in eukaryotes and demonstrate how the GRN controlling embryonic hematopoiesis acts as an irreversible bistable switch with low-pass noise filtering properties. We further used our model of the hematopoiesis network to reconcile discrepant experimental observations about the regulator Runx1 and explained how it limits HSC emergence in vitro. In the second project we investigated the Bacillus subtilis sporulation network and showed how a cascade of feed-forward loops downstream of the master regulatory Spo0A~P control cell-fate during starvation. We also identified a rate-responsive network module in the Spo0A regulon to explain why accelerated accumulation of Spo0A~P leads to a dramatic reduction in sporulation efficiency. Further we found that the arrangement of two sporulation network genes on opposite ends of the chromosome ties Spo0A~P activation to the DNA replication status. We were also able to show that the slowdown of cell growth is the primary starvation signal that determines sporulation cell-fates by controlling Spo0A~P activation. For the third project we built a detailed model of the σB network in Bacillus subtilis to
mechanistically explain the experimentally observed pulsatile response of this network under stress. We further showed that the same network architecture that enables this pulsatile response insulates the σB network from the effects of competition for cellular resources like RNA polymerase. The design principles identified in the studies of these networks are related to their topological structure and function rather than the specific genes and proteins that comprise them. As a result, we expect them to be widely applicable to and help in the study of a diverse array of other differentiation GRNs.
Advisors/Committee Members: Igoshin, Oleg A (advisor), Tabor, Jeffrey J (committee member), Bennett, Matthew R (committee member).
Subjects/Keywords: Differentiation; Gene Regulation
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Narula, J. (2015). Design Principles of Cellular Differentiation Regulatory Networks. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/88375
Chicago Manual of Style (16th Edition):
Narula, Jatin. “Design Principles of Cellular Differentiation Regulatory Networks.” 2015. Doctoral Dissertation, Rice University. Accessed March 01, 2021.
http://hdl.handle.net/1911/88375.
MLA Handbook (7th Edition):
Narula, Jatin. “Design Principles of Cellular Differentiation Regulatory Networks.” 2015. Web. 01 Mar 2021.
Vancouver:
Narula J. Design Principles of Cellular Differentiation Regulatory Networks. [Internet] [Doctoral dissertation]. Rice University; 2015. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/1911/88375.
Council of Science Editors:
Narula J. Design Principles of Cellular Differentiation Regulatory Networks. [Doctoral Dissertation]. Rice University; 2015. Available from: http://hdl.handle.net/1911/88375

Washington University in St. Louis
6.
Fiore, Christopher Michael.
Functional Identification and Characterization of cis-Regulatory Elements.
Degree: PhD, Biology & Biomedical Sciences (Computational & Systems Biology), 2015, Washington University in St. Louis
URL: https://openscholarship.wustl.edu/art_sci_etds/579
► Transcription is regulated through interactions between regulatory proteins, such as transcription factors (TFs), and DNA sequence. It is known that TFs act combinatorially in…
(more)
▼ Transcription is regulated through interactions between regulatory proteins, such as transcription factors (TFs), and DNA sequence. It is known that TFs act combinatorially in some cases to regulate transcription, but in which situations and to what degree is unclear. I first studied the contribution of TF binding sites to expression in mouse embryonic stem (ES) cells by using synthetic cis-regulatory elements (CREs). The synthetic CREs were comprised of combinations of binding sites for the pluripotency TFs Oct4, Sox2, Klf4, and Esrrb. A statistical thermodynamic model explained 72% of the variation in expression driven by these CREs. The high predictive power of this model depended on five TF interaction parameters, including favorable heterotypic interactions between Oct4 and Sox2, Klf4 and Sox2, and Klf4 and Esrrb. The model also included two unfavorable homotypic interaction parameters. These homotypic parameters help to explain the fact that synthetic CREs with mixtures of binding sites for various TFs drive much higher expression than multiple binding sites for the same TF. I then found that the expression of these synthetic CREs largely changes as ES cells differentiate down the neural lineage. However, CREs with no repeat binding sites drove similar levels of expression, suggesting that heterotypic interactions may be similar in the two conditions. In a separate set of experiments I interrogated the determinants of expression driven by genomic sequences previously segmented into classes based on chromatin features. A set of these sequences was assayed in K562 cells. As expected, we found that Enhancers and Weak Enhancers drove expression over background, while Repressed elements and Enhancers from another cell type did not. Unexpectedly, we found that Weak Enhancers drove higher expression than Enhancers, possibly based on their lower H3K36me3 and H3K27ac, which we found to be weakly associated with lower expression. Using a logistic regression model, we showed that matches to TF binding motifs were best able to predict active sequences, but chromatin features contributed significantly as well. These results demonstrate that interactions between certain combinations of pluripotency TFs, but not all combinations, are important to transcriptional
regulation. Furthermore, chromatin modifications can still contribute to predictions of expression even after accounting for binding site motifs. Better understanding of the process of cis-
regulation will allow us to predict which sequences can drive expression and how perturbations affect this expression.
Advisors/Committee Members: Barak A Cohen, Gary Stormo, Justin Fay, Joe Dougherty, Andrew Yoo.
Subjects/Keywords: cis-regulation, Gene Regulation, Regulatory Genomics; Biology
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Fiore, C. M. (2015). Functional Identification and Characterization of cis-Regulatory Elements. (Doctoral Dissertation). Washington University in St. Louis. Retrieved from https://openscholarship.wustl.edu/art_sci_etds/579
Chicago Manual of Style (16th Edition):
Fiore, Christopher Michael. “Functional Identification and Characterization of cis-Regulatory Elements.” 2015. Doctoral Dissertation, Washington University in St. Louis. Accessed March 01, 2021.
https://openscholarship.wustl.edu/art_sci_etds/579.
MLA Handbook (7th Edition):
Fiore, Christopher Michael. “Functional Identification and Characterization of cis-Regulatory Elements.” 2015. Web. 01 Mar 2021.
Vancouver:
Fiore CM. Functional Identification and Characterization of cis-Regulatory Elements. [Internet] [Doctoral dissertation]. Washington University in St. Louis; 2015. [cited 2021 Mar 01].
Available from: https://openscholarship.wustl.edu/art_sci_etds/579.
Council of Science Editors:
Fiore CM. Functional Identification and Characterization of cis-Regulatory Elements. [Doctoral Dissertation]. Washington University in St. Louis; 2015. Available from: https://openscholarship.wustl.edu/art_sci_etds/579

University of Saskatchewan
7.
Narayanan, Karthikeyan.
SCREENING AND CHARACTERIZATION OF ARABIDOPSIS THALIANA MUTANTS WITH ALTERED CAROTENOID PROFILE.
Degree: 2014, University of Saskatchewan
URL: http://hdl.handle.net/10388/ETD-2014-06-1601
► Carotenoids are organic pigments that are mainly found in the chloroplasts and chromoplasts of plants and other photosynthetic organisms. Carotenoid molecules containing oxygen, such as…
(more)
▼ Carotenoids are organic pigments that are mainly found in the chloroplasts and chromoplasts of plants and other photosynthetic organisms. Carotenoid molecules containing oxygen, such as lutein, violaxanthin and zeaxanthin are called xanthophylls and the rest containing un-oxygenated carotenoids are known as carotenes. Carotenoids form the integral part of the photosystem II LHC. Xanthophylls mainly aid in light harvesting and dissipation of harmful excess energy from excited chlorophyll molecules, thereby protecting chlorophyll from photo-degradation. The biosynthesis of carotenoids has been widely studied using plant and algae. However, the regulatory mechanisms involved in carotenoid metabolism need better understanding.
This thesis identified novel regulatory mechanisms involved in the carotenoid biosynthetic pathway using activation-tagged Arabidopsis mutants. Two screening methods, red seed coat screening and norflurazon resistance screening, were used in this study. Fourteen mutants were screened using red seed coat screening but a successful mutant characterization could not be performed due to the unavailability of mutants with a single copy T-DNA insertion.
Norflurazon screening identified eight mutants, out of which two mutants, KN203 and KN231, were characterized. The KN203 mutant had a defective keto-acyl CoA synthase 19
gene. KN203 mutant had lower carotenoid levels in the leaves and increased carotenoid levels in the mature seeds; the mutant was able to revert back to wild type phenotype after complementation of a functional KCS19
gene copy driven by native promoter. The fatty acid analysis indicated that the mutant KN203 had decreased MGDG and increased lysoPG, lysoPC and lysoPE content. Reduced carotenoid content in KN203 leaves was attributed to changes in fatty acid composition of chloroplast envelope membrane.
Mutant KN231 had a T-DNA insertion in a
gene encoding a RNA binding protein (RBP47C). KN231 leaf carotenoid levels were similar to wild type but their levels were significantly higher in their seeds. Two allelic mutants were selected to characterize the mutants. Overexpression of functional RBP47C in the mutants reverted to wild type phenotype in some overexpression mutants. A tandem repeat homologue of RBP47C, RBP47C’was identified. In-silico analysis predicted RBP47C to be a potential candidate for chloroplast localization.
Advisors/Committee Members: Khachatourians, George, Gruber, Margie, Hegedus, Dwayne, Gray, Gordon, Qiu, Xiao.
Subjects/Keywords: Carotneoids; RBP47; KCS19; Gene expression; Gene regulation
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Narayanan, K. (2014). SCREENING AND CHARACTERIZATION OF ARABIDOPSIS THALIANA MUTANTS WITH ALTERED CAROTENOID PROFILE. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/ETD-2014-06-1601
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):
Narayanan, Karthikeyan. “SCREENING AND CHARACTERIZATION OF ARABIDOPSIS THALIANA MUTANTS WITH ALTERED CAROTENOID PROFILE.” 2014. Thesis, University of Saskatchewan. Accessed March 01, 2021.
http://hdl.handle.net/10388/ETD-2014-06-1601.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Narayanan, Karthikeyan. “SCREENING AND CHARACTERIZATION OF ARABIDOPSIS THALIANA MUTANTS WITH ALTERED CAROTENOID PROFILE.” 2014. Web. 01 Mar 2021.
Vancouver:
Narayanan K. SCREENING AND CHARACTERIZATION OF ARABIDOPSIS THALIANA MUTANTS WITH ALTERED CAROTENOID PROFILE. [Internet] [Thesis]. University of Saskatchewan; 2014. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/10388/ETD-2014-06-1601.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Narayanan K. SCREENING AND CHARACTERIZATION OF ARABIDOPSIS THALIANA MUTANTS WITH ALTERED CAROTENOID PROFILE. [Thesis]. University of Saskatchewan; 2014. Available from: http://hdl.handle.net/10388/ETD-2014-06-1601
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
8.
Alasoo, Kaur.
Regulation of gene expression in macrophage immune response.
Degree: PhD, 2017, University of Cambridge
URL: https://www.repository.cam.ac.uk/handle/1810/263855
► Gene expression quantitative trait loci (eQTL) mapping studies can provide mechanistic insights into the functions of disease-associated variants. However, many eQTLs are cell type and…
(more)
▼ Gene expression quantitative trait loci (eQTL) mapping studies can provide mechanistic insights into the functions of disease-associated variants. However, many eQTLs are cell type and context specific. This is particularly relevant for immune cells, whose cellular function and behaviour can be substantially altered by external cues. Furthermore, understanding mechanisms behind eQTLs is hindered by the difficulty of identifying causal variants. We differentiated macrophages from induced pluripotent stem cells from 86 unrelated, healthy individuals derived as part of the Human Induced Pluripotent Stem Cells Initiative. We generated RNA-seq data from these cells in four experimental conditions: naïve, interferon- gamma (IFNɣ) treatment (18h), Salmonella infection (5h), and IFNγ treatment followed by Salmonella infection. We also measured chromatin accessibility with ATAC-seq in 31-42 individuals in the same four conditions. We detected gene expression QTLs (eQTLs) for 4326 genes, over 900 of which were condition-specific. We also detected a similar number of transcript ratio QTLs (trQTLs) that influenced mRNA processing and alternative splicing. Macrophage eQTLs and trQTLs were enriched for variants associated with Alzheimer’s disease, multiple autoimmune disorders and lipid traits. We also detected chromatin accessibility QTLs (caQTLs) for 14,602 accessible regions, including hundreds of long-range interactions. Joint analysis of eQTLs with caQTLs allowed us to greatly reduce the set of credible causal variants, often pinpointing to a single most likely variant. We found that caQTLs were less condition- specific than eQTLs and ~50% of the stimulation-specific eQTLs manifested on the chromatin level already in the naive cells. These observations might help to explain the discrepancy between strong enrichment of diseases associations in regulatory elements but only modest overlap with current eQTL studies, suggesting that many regulatory elements are in a ‘primed’ state waiting for an appropriate environmental signal before regulating gene expression.
Subjects/Keywords: Gene expression; Gene regulation; Chromatin; Genetics
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Alasoo, K. (2017). Regulation of gene expression in macrophage immune response. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/263855
Chicago Manual of Style (16th Edition):
Alasoo, Kaur. “Regulation of gene expression in macrophage immune response.” 2017. Doctoral Dissertation, University of Cambridge. Accessed March 01, 2021.
https://www.repository.cam.ac.uk/handle/1810/263855.
MLA Handbook (7th Edition):
Alasoo, Kaur. “Regulation of gene expression in macrophage immune response.” 2017. Web. 01 Mar 2021.
Vancouver:
Alasoo K. Regulation of gene expression in macrophage immune response. [Internet] [Doctoral dissertation]. University of Cambridge; 2017. [cited 2021 Mar 01].
Available from: https://www.repository.cam.ac.uk/handle/1810/263855.
Council of Science Editors:
Alasoo K. Regulation of gene expression in macrophage immune response. [Doctoral Dissertation]. University of Cambridge; 2017. Available from: https://www.repository.cam.ac.uk/handle/1810/263855
9.
Phillips, JL.
Regulation of ITGA6 and ITGB4 integrin genes by RUNX1 and epigenetic mechanisms.
Degree: 2017, University of Tasmania
URL: https://eprints.utas.edu.au/23900/1/Phillips_whole_thesis.pdf
;
Phillips,
JL
ORCID:
0000-0002-5559-3072
<https://orcid.org/0000-0002-5559-3072>
2017
,
'Regulation
of
ITGA6
and
ITGB4
integrin
genes
by
RUNX1
and
epigenetic
mechanisms',
PhD
thesis,
University
of
Tasmania.
► Disruption to regulatory mechanisms controlling gene expression is a hallmark of leukaemia, with disruption to transcription factors being one of the most prevalent. By identifying…
(more)
▼ Disruption to regulatory mechanisms controlling gene expression is a hallmark of leukaemia, with disruption to transcription factors being one of the most prevalent. By identifying the gene expression profile under the control of these transcription factors, and understanding how the target genes are regulated, critical insight can be gained into the role of these transcription factors in haematopoiesis, as well as their role in leukaemia development. Evidence presented here suggests that the RUNX1 transcription factor regulates the expression of the α6β4 integrin receptor in haematopoietic cells by controlling the integrin genes ITGA6 and ITGB4. Engagement of integrin receptors with extracellular matrix components of the bone marrow and haematopoietic tissues plays an essential role in haematopoiesis. Integrin expression is also altered in many leukaemias, however the regulation of integrin gene expression both in normal and disease states has remained largely unexplored.
Data presented here identified ITGA6 and ITGB4 as novel target genes of the RUNX1 transcription factor in myeloid cells. RUNX1 was found to bind to the promoter regions of ITGA6 and ITGB4 in myeloid cells in ChIP assays. Furthermore, RUNX1 had a functional effect on both of the promoters in reporter assays. RUNX1 increased the activity of both promoters, while RUNX1-ETO, which is produced by a common chromosomal translocation in leukaemic cells, repressed promoter activity, consistent with its well-characterised role as a transcriptional repressor.
While RUNX1 is commonly described as a sequence-specific DNA binding protein that binds to the consensus motif TGT/cGGT, it is becoming evident that the regulation of genes by RUNX1 is more complex than this and RUNX1 can regulate its target genes through a variety of mechanisms. Evidence presented here suggests that RUNX1 regulates the ITGA6 and ITGB4 integrin genes via two distinct mechanisms. RUNX1 was found to regulate the ITGA6 promoter through a consensus RUNX1 binding motif and RUNX1 activation of the promoter was dependent on this motif, in keeping with the traditional model of RUNX1 function described in the literature. In contrast, RUNX1 does not target the ITGB4 promoter through a consensus sequence motif and may be recruited indirectly to the promoter by other haematopoietic transcription factors.
Furthermore, the data presented here suggest that efficient regulation of the ITGB4 gene may require interactions between the promoter and an upstream enhancer. RUNX1 was also found to interact with the ITGB4 enhancer, and similarly to the promoter, these interactions do not require a RUNX1 consensus binding motif and may involve recruitment by other transcription factors. Recent evidence suggests that the traditional model of RUNX1 function through a consensus binding motif may represent only a small proportion of RUNX1 target genes. Genome-wide analysis suggests that a significant proportion of RUNX1 recruitment to DNA occurs in the absence of consensus binding motifs, as shown here for ITGB4.…
Subjects/Keywords: gene regulation; integrins; epigenetics RUNX1
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Phillips, J. (2017). Regulation of ITGA6 and ITGB4 integrin genes by RUNX1 and epigenetic mechanisms. (Thesis). University of Tasmania. Retrieved from https://eprints.utas.edu.au/23900/1/Phillips_whole_thesis.pdf ; Phillips, JL ORCID: 0000-0002-5559-3072 <https://orcid.org/0000-0002-5559-3072> 2017 , 'Regulation of ITGA6 and ITGB4 integrin genes by RUNX1 and epigenetic mechanisms', PhD thesis, University of Tasmania.
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):
Phillips, JL. “Regulation of ITGA6 and ITGB4 integrin genes by RUNX1 and epigenetic mechanisms.” 2017. Thesis, University of Tasmania. Accessed March 01, 2021.
https://eprints.utas.edu.au/23900/1/Phillips_whole_thesis.pdf ; Phillips, JL ORCID: 0000-0002-5559-3072 <https://orcid.org/0000-0002-5559-3072> 2017 , 'Regulation of ITGA6 and ITGB4 integrin genes by RUNX1 and epigenetic mechanisms', PhD thesis, University of Tasmania..
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Phillips, JL. “Regulation of ITGA6 and ITGB4 integrin genes by RUNX1 and epigenetic mechanisms.” 2017. Web. 01 Mar 2021.
Vancouver:
Phillips J. Regulation of ITGA6 and ITGB4 integrin genes by RUNX1 and epigenetic mechanisms. [Internet] [Thesis]. University of Tasmania; 2017. [cited 2021 Mar 01].
Available from: https://eprints.utas.edu.au/23900/1/Phillips_whole_thesis.pdf ; Phillips, JL ORCID: 0000-0002-5559-3072 <https://orcid.org/0000-0002-5559-3072> 2017 , 'Regulation of ITGA6 and ITGB4 integrin genes by RUNX1 and epigenetic mechanisms', PhD thesis, University of Tasmania..
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Phillips J. Regulation of ITGA6 and ITGB4 integrin genes by RUNX1 and epigenetic mechanisms. [Thesis]. University of Tasmania; 2017. Available from: https://eprints.utas.edu.au/23900/1/Phillips_whole_thesis.pdf ; Phillips, JL ORCID: 0000-0002-5559-3072 <https://orcid.org/0000-0002-5559-3072> 2017 , 'Regulation of ITGA6 and ITGB4 integrin genes by RUNX1 and epigenetic mechanisms', PhD thesis, University of Tasmania.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Tasmania
10.
Apps, LD.
Regulation of inducible immune gene expression in T cells compared to macrophages.
Degree: 2014, University of Tasmania
URL: https://eprints.utas.edu.au/18558/1/Whole-Apps-thesis.pdf
► The initiation, duration and resolution of an appropriate immune response is vital for defending the host against invading pathogens, toxins and cancerous cells. Such immune…
(more)
▼ The initiation, duration and resolution of an appropriate immune response is vital for defending the host against invading pathogens, toxins and cancerous cells. Such immune responses are reliant on the cooperative action of multiple cell types and the co-ordinated regulation of gene expression programs, which direct immune function. Inducible gene expression upon immune activation is determined by the complex interaction between transcription factors, the chromatin structure and chromatin modifying/remodelling factors at the regulatory regions of immune genes. The NF-κB transcription factor c-Rel is a key regulator of gene expression programs within the immune system. c-Rel regulates expression of cytokines and transcription factors during immune cell activation and is essential for the correct function of immune cells from divergent cell lineages. These differentiated cells are highly specialised and have a diverse range of functions requiring precise regulation of their gene expression profiles for targeted responses. This study explores the role of c-Rel in divergent lymphocyte and macrophage lineages.
c-Rel has previously been shown to instigate chromatin remodelling events required for activation of the GM-CSF gene in T cells. Activation involves the depletion of hyper-acetylated histones from the promoter region of the gene, mediated by the chromatin remodelling protein BRG1. This study shows that activation of the GM-CSF gene is also c-Rel dependent in macrophages, however the gene promoter is not marked by acetylated chromatin and no loss of H3 is detected in association with activation. These findings suggest that whilst the GM-CSF gene is expressed in both T cells and macrophages, activation is regulated by fundamentally different mechanisms in the two cell types. The hypothesis underlying this study is that during the process of differentiation lineage specific chromatin structure is established at inducible gene promoters and that this chromatin structure largely dictates the cooperative regulation of gene expression through interaction with transcription factors, structural proteins and chromatin remodelling enzymes.
Using genome-wide data sets, a cohort of immune genes which are regulated by c-Rel were identified. These genes were further categorised into BRG1 independent and dependent genes. The activation requirements of these genes were examined in both T cells and macrophages to determine whether the switch in regulatory control identified for the GM-CSF gene is a common feature of genes that are co-expressed by these cell types, and to characterise the mechanisms underlying this fundamental difference in regulation. Data presented in this thesis demonstrates that several genes undergo switches in the requirements for gene expression between the two cell types. The analysis of chromatin structure indicates that these differences in activation kinetics are reflective of the basal chromatin accessibility established at the genes promoter regions. Furthermore, the extent of chromatin remodelling…
Subjects/Keywords: Epigenetics; gene regulation; immune response
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Apps, L. (2014). Regulation of inducible immune gene expression in T cells compared to macrophages. (Thesis). University of Tasmania. Retrieved from https://eprints.utas.edu.au/18558/1/Whole-Apps-thesis.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):
Apps, LD. “Regulation of inducible immune gene expression in T cells compared to macrophages.” 2014. Thesis, University of Tasmania. Accessed March 01, 2021.
https://eprints.utas.edu.au/18558/1/Whole-Apps-thesis.pdf.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Apps, LD. “Regulation of inducible immune gene expression in T cells compared to macrophages.” 2014. Web. 01 Mar 2021.
Vancouver:
Apps L. Regulation of inducible immune gene expression in T cells compared to macrophages. [Internet] [Thesis]. University of Tasmania; 2014. [cited 2021 Mar 01].
Available from: https://eprints.utas.edu.au/18558/1/Whole-Apps-thesis.pdf.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Apps L. Regulation of inducible immune gene expression in T cells compared to macrophages. [Thesis]. University of Tasmania; 2014. Available from: https://eprints.utas.edu.au/18558/1/Whole-Apps-thesis.pdf
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Texas A&M University
11.
Malik, Indranil.
In Vivo Consequences of Altered Pol II Catalysis.
Degree: PhD, Biochemistry, 2017, Texas A&M University
URL: http://hdl.handle.net/1969.1/165890
► Gene transcription by RNA polymerase II (Pol II) is an essential process. Using Saccharomyces cerevisiae as a model system, our lab has previously identified and…
(more)
▼ Gene transcription by RNA polymerase II (Pol II) is an essential process. Using Saccharomyces cerevisiae as a model system, our lab has previously identified and partially characterized Pol II activity mutants that can alter catalysis rate to faster or slower than wild type in vitro. In my dissertation research I use a set of these Pol II activity mutants to determine consequences of altered catalysis rate on polymerase functions, co-transcriptional pre-mRNA processing and
gene expression in vivo. I show that alteration in Pol II catalytic rate, either increase or decrease, leads to a decreased Pol II occupancy and an apparent reduction in elongation rate on a commonly used reporter
gene in vivo. Measurement of in vivo elongation rate on this reporter requires transcriptional shutoff followed by ChIP. I discover that some Pol II catalytic mutants can compromise the kinetics of transcription shutoff by glucose, which is generally assumed to be unaffected by transcription mutants. Further, I show that Pol II catalytic mutants affect model
gene expression and the effects on
gene expression are exacerbated with increased promoter strength and
gene length. My results suggest that
gene expression defects in the Pol II mutants may in part result from defective mRNA processing. Additionally, I show that mRNA half-lives for that model
gene are increased in Pol II mutant strains and the magnitude of half-life changes correlate both with mutants’ growth and the magnitude of reporter
gene expression defects. Finally, I test if altered Pol II elongation sensitizes cells to nucleotide depletion and find that Pol II mutants and several elongation factor mutants respond to GTP starvation similarly to wild type and that putative elongation defects are not likely to drive the cellular response to limiting GTP. Altogether my findings reveal wide-ranging in vivo effects of Pol II catalytic mutants, which will be critical for precise use of these Pol II catalytic mutants in
gene regulation studies.
Advisors/Committee Members: Kaplan, Craig D (advisor), Rye, Hays (committee member), Polymenis, Michael (committee member), Sachs, Matthew S (committee member).
Subjects/Keywords: Transcription; RNA polymerase; Gene regulation
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Malik, I. (2017). In Vivo Consequences of Altered Pol II Catalysis. (Doctoral Dissertation). Texas A&M University. Retrieved from http://hdl.handle.net/1969.1/165890
Chicago Manual of Style (16th Edition):
Malik, Indranil. “In Vivo Consequences of Altered Pol II Catalysis.” 2017. Doctoral Dissertation, Texas A&M University. Accessed March 01, 2021.
http://hdl.handle.net/1969.1/165890.
MLA Handbook (7th Edition):
Malik, Indranil. “In Vivo Consequences of Altered Pol II Catalysis.” 2017. Web. 01 Mar 2021.
Vancouver:
Malik I. In Vivo Consequences of Altered Pol II Catalysis. [Internet] [Doctoral dissertation]. Texas A&M University; 2017. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/1969.1/165890.
Council of Science Editors:
Malik I. In Vivo Consequences of Altered Pol II Catalysis. [Doctoral Dissertation]. Texas A&M University; 2017. Available from: http://hdl.handle.net/1969.1/165890

University of Adelaide
12.
Raimondo, Anne.
Identification of downstream target genes and analysis of obesity-related variants of the bHLH/PAS transcription factor single-minded 1.
Degree: 2011, University of Adelaide
URL: http://hdl.handle.net/2440/73199
► Single-minded 1 (SIM1) is a basic Helix-Loop-Helix/PER-ARNT-SIM (bHLH/PAS) transcription factor essential for survival in mice. The early post-natal lethality exhibited by Sim1⁻ʹ⁻ mice is believed…
(more)
▼ Single-minded 1 (SIM1) is a basic Helix-Loop-Helix/PER-ARNT-SIM (bHLH/PAS) transcription factor essential for survival in mice. The early post-natal lethality exhibited by Sim1⁻ʹ⁻ mice is believed to be the consequence of severely compromised hypothalamus development, although the contribution of reduced SIM1 signalling in the numerous other tissues in which it is expressed has never been formally investigated. The presence of a single Sim1 allele is sufficient to avoid this perinatal lethality, and instead confers an early onset, hyperphagic obesity phenotype, potentially via disruption of critical intracellular signalling pathways that are activated in Sim1-expressing hypothalamic neurons in response to food intake. Similar correlations between reduced SIM1
gene dosage and severe obesity have also been documented in humans. Alterations in SIM1 expression and/or function therefore have important implications in health and disease, and warrant a detailed investigation into the downstream target genes and regulatory behaviours of this critical transcription factor, which are thus far almost entirely lacking in the literature. The studies presented in this thesis describe a twofold approach to dissecting the
gene regulatory properties of the SIM1 protein. Firstly, we optimised and performed a range of functional assays, including a cell-based luciferase reporter
gene assay, a subcellular localisation assay, a co-immunoprecipitation assay, and an electrophoretic mobility shift assay, which were designed to assess the contribution of nineteen unique point mutations within the SIM1 protein sequence to altered SIM1 expression and behaviour. These nineteen mutations were identified in multiple cohorts of severely obese humans, and therefore represent potentially pathogenic alterations in the SIM1 sequence. Indeed, we observed a significant loss of function for many of these variants in luciferase reporter
gene assays relative to wild type SIM1. The severe loss of function observed for one of these variants, SIM1 T292A, could be further attributed to altered subcellular localisation, thus impacting on its ability to form a stable heterodimer with ARNT2 in co-immunoprecipitation experiments. Secondly, we performed microarray studies on cultured kidney-derived cells inducibly overexpressing Myc-tagged SIM1 and its obligate partner factor ARNT2, and subsequently identified several genes that selectively responded to SIM/ARNT2 overexpression in this context. Further validation in hypothalamus-derived cultured cells highlighted Myomesin 2 (Myom2) as a potentially genuine downstream SIM1 target
gene in both kidney and hypothalamus. We also present data that are the first to indicate Somatostatin (Ss) as a hypothalamic target
gene regulated by SIM1 in a cell-autonomous manner. These data are among the first to dissect the downstream target genes and regulatory properties of the SIM1 protein, and therefore make an important contribution to our understanding of the molecular basis to the hyperphagic obesity exhibited by Sim1⁺ʹ⁻ mice.…
Advisors/Committee Members: Whitelaw, Murray Leslie (advisor), Chapman-Smith, Anne (advisor), Koblar, Simon Andrea (advisor), School of Molecular and Biomedical Science (school).
Subjects/Keywords: transcription; gene regulation; obesity
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Raimondo, A. (2011). Identification of downstream target genes and analysis of obesity-related variants of the bHLH/PAS transcription factor single-minded 1. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/73199
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):
Raimondo, Anne. “Identification of downstream target genes and analysis of obesity-related variants of the bHLH/PAS transcription factor single-minded 1.” 2011. Thesis, University of Adelaide. Accessed March 01, 2021.
http://hdl.handle.net/2440/73199.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Raimondo, Anne. “Identification of downstream target genes and analysis of obesity-related variants of the bHLH/PAS transcription factor single-minded 1.” 2011. Web. 01 Mar 2021.
Vancouver:
Raimondo A. Identification of downstream target genes and analysis of obesity-related variants of the bHLH/PAS transcription factor single-minded 1. [Internet] [Thesis]. University of Adelaide; 2011. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/2440/73199.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Raimondo A. Identification of downstream target genes and analysis of obesity-related variants of the bHLH/PAS transcription factor single-minded 1. [Thesis]. University of Adelaide; 2011. Available from: http://hdl.handle.net/2440/73199
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – San Francisco
13.
Dalton, Ryan P.
Chemoreceptor Feedback by the Unfolded Protein Response.
Degree: Neuroscience, 2015, University of California – San Francisco
URL: http://www.escholarship.org/uc/item/0z78b1sw
► Each olfactory sensory neuron (OSN) expresses exactly one olfactory receptor (OR) gene, a feature which requires both a limiting or inefficient process of OR transcriptional…
(more)
▼ Each olfactory sensory neuron (OSN) expresses exactly one olfactory receptor (OR) gene, a feature which requires both a limiting or inefficient process of OR transcriptional activation and a subsequent process of OR feedback. Monogenic expression of ORs is thought to underlie the ability of animals to sensitively and specifically identify innumerable cues, and therefore understanding how olfactory receptor genes are transcriptionally activated and how they elicit feedback are problems of paramount importance in understanding the development of the olfactory system. The thesis project presented herein demonstrates that OR feedback is elicited through a surprising ability of olfactory receptor protein to elicit the unfolded protein response (UPR), a ubiquitous and highly-conserved proteostatic signaling pathway that is typically thought to be responsive to stress conditions. Activation of the UPR by OR expression in OSNs drives translation of a transcription factor specific to chemosensory neurons, resulting in stabilization of OR choice and monogenic OR expression, OSN maturation, and a termination of further OR choice. This signaling pathway is general to vomeronasal sensory neurons (VSNs) and is most likely also found in other sensory cells with limited patters of G protein-coupled receptor expression including neurons of the trigeminal ganglion and the taste receptor cells of the tongue. Finally, the means by which ORs and vomeronasal receptors (VRs) activate the UPR is shown, with ORs and VRs activating the UPR indirectly and directly, respectively. Thus, while these receptors have divergent mechanisms of UPR activation, they have a convergent use of the UPR in order to coordinate monogenic receptor expression and to time development to the appearance of the chemoreceptor.
Subjects/Keywords: Cellular biology; gene regulation; olfaction
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Dalton, R. P. (2015). Chemoreceptor Feedback by the Unfolded Protein Response. (Thesis). University of California – San Francisco. Retrieved from http://www.escholarship.org/uc/item/0z78b1sw
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):
Dalton, Ryan P. “Chemoreceptor Feedback by the Unfolded Protein Response.” 2015. Thesis, University of California – San Francisco. Accessed March 01, 2021.
http://www.escholarship.org/uc/item/0z78b1sw.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Dalton, Ryan P. “Chemoreceptor Feedback by the Unfolded Protein Response.” 2015. Web. 01 Mar 2021.
Vancouver:
Dalton RP. Chemoreceptor Feedback by the Unfolded Protein Response. [Internet] [Thesis]. University of California – San Francisco; 2015. [cited 2021 Mar 01].
Available from: http://www.escholarship.org/uc/item/0z78b1sw.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Dalton RP. Chemoreceptor Feedback by the Unfolded Protein Response. [Thesis]. University of California – San Francisco; 2015. Available from: http://www.escholarship.org/uc/item/0z78b1sw
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
14.
Biette, Kelly Marie.
Enhancer Interactions in Developmental Gene Regulation.
Degree: PhD, 2019, Harvard University
URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029813
► When and where a gene is expressed during development is a critical determinant of cell identity and transcriptional mis-regulation is a common driver of diverse…
(more)
▼ When and where a gene is expressed during development is a critical determinant of cell identity and transcriptional mis-regulation is a common driver of diverse disease states. The spatial and temporal expression of animal genes is controlled by enhancers, sequences of DNA that are bound by transcription factors (TFs) and direct the pattern, timing, and level of gene expression. Many developmental genes are surrounded by multiple enhancers, each of which directs a subset of the overall gene expression pattern, allowing the gene to be turned on at different stages or in different tissues throughout the lifetime of the organism. However, it remains unclear how the promoter integrates information from across a gene locus such that select enhancers are active at the right times, in the right cells, and in the right combinations.
Enhancers have long been described as “modules” that function independent of distance from and orientation to the promoter and other regulatory sequences. However, there is increasing evidence in the field that interactions between enhancers and other regulatory sequences are more common than initially appreciated. The current challenge is to understand the prevalence and functional consequences of these interactions on gene expression, both at the level of a single locus and at longer genomic scales.
We challenged this canonical view of enhancer modularity with computational models and quantitative experiments using two enhancers of the even-skipped locus in Drosophila melanogaster blastoderm embryos. Using controlled molecular biology and high-resolution imaging, we moved enhancers relative to each other in reporter constructs and deleted them from the endogenous locus to demonstrate that interactions between enhancers have functional consequences on gene expression. These results argue that mechanisms of gene regulation operate at the locus-level to control the precise expression of this key developmental gene. The evidence presented herein suggests that the classical model by which enhancers function independently of surrounding sequences is too simplistic and lays the groundwork for future studies that identify the mechanisms by which information from many enhancers is integrated by a single promoter to produce precise and robust gene expression patterns throughout development.
Systems Biology
Advisors/Committee Members: Springer, Michael (advisor), Kirschner, Marc (committee member), Adelman, Karen (committee member), Fuxman Bass, Juan (committee member).
Subjects/Keywords: enhancers; gene regulation; transcription; drosophila
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Biette, K. M. (2019). Enhancer Interactions in Developmental Gene Regulation. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029813
Chicago Manual of Style (16th Edition):
Biette, Kelly Marie. “Enhancer Interactions in Developmental Gene Regulation.” 2019. Doctoral Dissertation, Harvard University. Accessed March 01, 2021.
http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029813.
MLA Handbook (7th Edition):
Biette, Kelly Marie. “Enhancer Interactions in Developmental Gene Regulation.” 2019. Web. 01 Mar 2021.
Vancouver:
Biette KM. Enhancer Interactions in Developmental Gene Regulation. [Internet] [Doctoral dissertation]. Harvard University; 2019. [cited 2021 Mar 01].
Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029813.
Council of Science Editors:
Biette KM. Enhancer Interactions in Developmental Gene Regulation. [Doctoral Dissertation]. Harvard University; 2019. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029813

University of Edinburgh
15.
Buckle, Adam James.
Regulatory architecture of the Pax6 locus.
Degree: PhD, 2014, University of Edinburgh
URL: http://hdl.handle.net/1842/16878
► Pax6 is a highly conserved developmental regulator with a complex temporal, spatial and quantitative expression pattern, that is crucial for correct development of the central…
(more)
▼ Pax6 is a highly conserved developmental regulator with a complex temporal, spatial and quantitative expression pattern, that is crucial for correct development of the central nervous system, the eye, and pancreas. Accordingly, the Pax6 gene resides in a complex genomic locus containing a large array of long-range tissue-specific cis-regulatory elements primarily identified through multispecies sequence conservation and reporter studies. I have set out to understand how the chromatin architecture of the locus contributes to the mechanism and specificity of cis-regulatory interactions. As well as addressing whether the DNA looping model for regulatory interactions applies to the mouse Pax6 locus, I will identify which elements facilitate such interactions and if they vary between cell types. Utilising ChIP-array technology the distribution and variability of key regulatory histone modifications and factors were assessed in a set of Pax6 expressing and non-expressing mouse cell lines, acting as models for different regulatory states of the locus. Work in other loci suggests a key role for CTCF and cohesin (subunit Rad21) in chromatin organisation and long distance regulatory interactions. ChIP-chip for CTCF/Rad21 across the Pax6 locus identified numerous sites within the gene and at distal regulatory locations. The majority of these sites are cell type invariable. The active enhancer modification H3K27ac identified both known and several novel putative enhancer elements distributed through the locus that are highly cell type specific. A subset of CTCF/Rad21 sites also acquire the active enhancer modification H3K27ac in a cell type dependent manor, suggesting that CTCF/Rad21 may facilitate looping to the target gene from these sites. Using reporter based assays, putative regulatory elements marked by the looping factors and active histone modifications showed a diverse range of functional activities. Unexpectedly only 3 of the 7 CTCF sites tested showed classical insulator activity in an enhancer blocking reporter assay. Surprisingly the strongest insulator tested resided within intron 7 the Pax6 gene. Other CTCF/Rad21 sites were neutral or enhancers in the insulator assay. This reveals the disparity between predicting regulatory properties using ChIP binding profiles alone and the actual outcome of functional reporter experiments. A novel element, CTCF6 showed a ChIP signature of CTCF/Rad21/H3K27ac in all Pax6 expressing tissues, and functioned as a strong enhancer in transient transfection and stable LacZ reporter assays. CTCF6 recapitulated a broad range of Pax6 expression patterns, at multiple embryonic stages, including the brain, neural tube and pancreas. A second novel element, E-120 identified in the pancreatic derived cell line, drove stable embryonic reporter expression in the embryonic pancreas and sub set of brain regions. Together this has expanded the repertoire and size of Pax6’s regulatory landscape particular in the upstream region. Chromatin conformation capture (3C) was used to characterise the…
Subjects/Keywords: 572.8; Pax6; gene regulation; chromatin
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Buckle, A. J. (2014). Regulatory architecture of the Pax6 locus. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/16878
Chicago Manual of Style (16th Edition):
Buckle, Adam James. “Regulatory architecture of the Pax6 locus.” 2014. Doctoral Dissertation, University of Edinburgh. Accessed March 01, 2021.
http://hdl.handle.net/1842/16878.
MLA Handbook (7th Edition):
Buckle, Adam James. “Regulatory architecture of the Pax6 locus.” 2014. Web. 01 Mar 2021.
Vancouver:
Buckle AJ. Regulatory architecture of the Pax6 locus. [Internet] [Doctoral dissertation]. University of Edinburgh; 2014. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/1842/16878.
Council of Science Editors:
Buckle AJ. Regulatory architecture of the Pax6 locus. [Doctoral Dissertation]. University of Edinburgh; 2014. Available from: http://hdl.handle.net/1842/16878

Rice University
16.
Ruths, Troy.
Population Regulomics: Applying population genetics to the cis-regulome.
Degree: PhD, Engineering, 2014, Rice University
URL: http://hdl.handle.net/1911/77508
► Population genetics provides a mathematical and computational framework for understanding and modeling evolutionary processes, and so it is vital for the investigation of biological systems.…
(more)
▼ Population genetics provides a mathematical and computational framework for understanding
and modeling evolutionary processes, and so it is vital for the investigation
of biological systems. In its current state, molecular population genetics is exclusively
focused on molecular sequences (DNA, RNA, or amino acid sequences), where
all application-ready simulators and analytic measures work only on sequence data.
Consequently, in the early 2000s, when technologies became available to sequence
entire genomes, population genetic approaches were naturally applied to mine out
signatures of selection and conservation, resulting in the subfi eld of population genomics.
Nearly every present genome project applies population genomic techniques
to identify functional information and genome structure.
Recent technologies have ushered in a similar wave of genetic information, this
time focusing on biological mechanisms operating above the genome, most notably
on
gene regulation (regulatory networks). In this work, I develop a molecular population
genetics approach for
gene regulation, called population regulomics, which
includes simulators and analytic measurements that operate on populations of regulatory
networks. I conducted extensive data analyses to connect the genome with the
cis-regulome, developed computationally effi cient simulators, and adapted population
genetic measurements on sequence to the regulatory network. By connecting genomic
information to cis-
regulation, we may apply the wealth of knowledge at the genome
level to observed patterns at the regulatory level with unknown evolutionary origin.
I demonstrate that by applying population regulomics to the E. coli cis-regulatory
network, for the rst time we are able to quantify the evolutionary origins of topological
patterns and reveal the surprising amount of neutral signal in the bacterial
cis-regulome. Since regulatory networks play a central role in cellular functioning and,
consequently, organismal fitness, this new sub-fi eld of population regulomics promises
to shed the light of evolution on regulatory mechanisms and, more broadly, on the
genetic mechanisms underlying the various phenotypes.
Advisors/Committee Members: Nakhleh, Luay K. (advisor), Jermaine, Christopher M. (committee member), Kavraki, Lydia E. (committee member), Kohn, Michael H. (committee member).
Subjects/Keywords: Population genetics; Simulation; Gene regulation
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ruths, T. (2014). Population Regulomics: Applying population genetics to the cis-regulome. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/77508
Chicago Manual of Style (16th Edition):
Ruths, Troy. “Population Regulomics: Applying population genetics to the cis-regulome.” 2014. Doctoral Dissertation, Rice University. Accessed March 01, 2021.
http://hdl.handle.net/1911/77508.
MLA Handbook (7th Edition):
Ruths, Troy. “Population Regulomics: Applying population genetics to the cis-regulome.” 2014. Web. 01 Mar 2021.
Vancouver:
Ruths T. Population Regulomics: Applying population genetics to the cis-regulome. [Internet] [Doctoral dissertation]. Rice University; 2014. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/1911/77508.
Council of Science Editors:
Ruths T. Population Regulomics: Applying population genetics to the cis-regulome. [Doctoral Dissertation]. Rice University; 2014. Available from: http://hdl.handle.net/1911/77508

University of New Mexico
17.
Morriss, Ginny.
Identification of the wings apart transcriptional unit in Drosophila melanogaster.
Degree: UNM Biology Department, 2012, University of New Mexico
URL: https://digitalrepository.unm.edu/biol_etds/84
► Muscle development is an evolutionarily conserved process. Mechanisms that govern the development of specific muscles in invertebrates can inform our understanding of how vertebrate muscles…
(more)
▼ Muscle development is an evolutionarily conserved process. Mechanisms that govern the development of specific muscles in invertebrates can inform our understanding of how vertebrate muscles form. Understanding these processes allows us to translate developmental mechanisms to disease pathogenesis, as similar genes and developmental processes are affected by these diseases. In this dissertation, CG14614 is identified as the
gene responsible for the wings apart phenotype in Drosophila melanogaster. This mutation leads to a loss of the adult jump muscle (TDT) in most cases and a greater than 60% reduction in muscle fibers in its least severe form. wap mutants fail to properly form neuromuscular junctions to the TDT, resulting in degeneration of the muscle.
Regulation of Myocyte enhancer factor 2 (Mef2) expression in the developing mesoderm, which gives rise to somatic, visceral, and cardiac muscle, by the transcription factors Twist and Mad was also investigated. Our results indicate these are both involved in
regulation of the Mef2 enhancer but additional complexity exists in its
regulation that remains to be fully elucidated.
Advisors/Committee Members: Cripps, Richard, Stricker, Stephen, Takacs-Vesbach, Cristina, Gelbart, William.
Subjects/Keywords: myogenesis; development; gene regulation; Drosophila
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Morriss, G. (2012). Identification of the wings apart transcriptional unit in Drosophila melanogaster. (Doctoral Dissertation). University of New Mexico. Retrieved from https://digitalrepository.unm.edu/biol_etds/84
Chicago Manual of Style (16th Edition):
Morriss, Ginny. “Identification of the wings apart transcriptional unit in Drosophila melanogaster.” 2012. Doctoral Dissertation, University of New Mexico. Accessed March 01, 2021.
https://digitalrepository.unm.edu/biol_etds/84.
MLA Handbook (7th Edition):
Morriss, Ginny. “Identification of the wings apart transcriptional unit in Drosophila melanogaster.” 2012. Web. 01 Mar 2021.
Vancouver:
Morriss G. Identification of the wings apart transcriptional unit in Drosophila melanogaster. [Internet] [Doctoral dissertation]. University of New Mexico; 2012. [cited 2021 Mar 01].
Available from: https://digitalrepository.unm.edu/biol_etds/84.
Council of Science Editors:
Morriss G. Identification of the wings apart transcriptional unit in Drosophila melanogaster. [Doctoral Dissertation]. University of New Mexico; 2012. Available from: https://digitalrepository.unm.edu/biol_etds/84

University of Minnesota
18.
Lang, Kevin.
Transcriptional regulation of incompatibility type A/C plasmids.
Degree: PhD, Comparative and Molecular Biosciences, 2015, University of Minnesota
URL: http://hdl.handle.net/11299/174866
► Plasmids are extrachromosomal DNA elements that often carry beneficial phenotypes for the bacterial host. Incompatibility type A/C (IncA/C) plasmids are large (~100 ~ 200 kilobases…
(more)
▼ Plasmids are extrachromosomal DNA elements that often carry beneficial phenotypes for the bacterial host. Incompatibility type A/C (IncA/C) plasmids are large (~100 ~ 200 kilobases (kb)), conjugative plasmids that are carried by Gram-negative bacteria. IncA/C plasmids often carry numerous genes that confer resistance to antimicrobials and have been isolated from many types of bacteria that pose significant risks in both human and animal medicine. Although IncA/C plasmids have been described in the literature for many years, little is known about their basic biology. For the past decade, many fully sequenced IncA/C variants have been described. There has been a lack of work concerning core functions of these plasmids, such as, replication, conjugative transfer and maintenance. This dissertation focuses on how these plasmids are regulated on a transcriptional level. We used pAR060302, a prototypical IncA/C plasmid, to conduct several experiments investigating exactly what genes are transcribed and how different conditions affect their transcriptional landscape. RNA-Seq was used to understand how antimicrobial exposure can affect the way genes are expressed on IncA/C plasmids. We found that, under the conditions we tested, antimicrobials have little effect on the transcription of genes on pAR060302. However, this initial study was the first to explore genes carried IncA/C plasmids in terms of their expression. Further RNA-Seq experiments were carried out in several different bacterial genera all carrying the same IncA/C plasmid, pAR060302. These experiments attempted to characterize how a broad host-range plasmid, such as IncA/C, might be differentially regulated in different hosts. We found that only subtle changes occur in the expression of plasmid genes. Carriage of IncA/C plasmids was found to have diverse effects on chromosomal gene expression. Genes involved in 2-carbon metabolism in Escherichia coli are up-regulated due to plasmid carriage. Our results suggest that plasmid encoded factors might serve varying levels of importance depending on the host chromosomal background. Experiments were carried out on E. coli carrying plasmids with mutations in a group of predicted transcriptional regulators to determine their function. We identified the positive regulators of conjugative transfer in IncA/C plasmids, acaD and acaC. We also found a repressor of transfer, acr2, which encodes an H-NS-like protein. We further show that acr2 might regulate genes beyond those that are involved in conjugative transfer. This dissertation builds on our understanding on what mechanisms are important for the maintenance of large plasmids in Gram-negative bacteria. Understanding how plasmids might specifically tune host metabolism to improve competitive fitness would impact what evolutionary processes were involved in their emergence. Characterization of regulatory networks that govern core plasmid processes, such as conjugation, might assist in the development of new models of how these plasmids disseminate throughout bacterial…
Subjects/Keywords: antibiotic resistance; gene regulation; Plasmids
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lang, K. (2015). Transcriptional regulation of incompatibility type A/C plasmids. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/174866
Chicago Manual of Style (16th Edition):
Lang, Kevin. “Transcriptional regulation of incompatibility type A/C plasmids.” 2015. Doctoral Dissertation, University of Minnesota. Accessed March 01, 2021.
http://hdl.handle.net/11299/174866.
MLA Handbook (7th Edition):
Lang, Kevin. “Transcriptional regulation of incompatibility type A/C plasmids.” 2015. Web. 01 Mar 2021.
Vancouver:
Lang K. Transcriptional regulation of incompatibility type A/C plasmids. [Internet] [Doctoral dissertation]. University of Minnesota; 2015. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/11299/174866.
Council of Science Editors:
Lang K. Transcriptional regulation of incompatibility type A/C plasmids. [Doctoral Dissertation]. University of Minnesota; 2015. Available from: http://hdl.handle.net/11299/174866

Queens University
19.
Garand, Mathieu.
Regulation of the Gene Encoding Thrombin-Activable Fibrinolysis Inhibitor
.
Degree: Biochemistry, 2010, Queens University
URL: http://hdl.handle.net/1974/5522
► Disequilibrium between coagulation and fibrinolysis can lead to severe haemostatic disorders such as thrombosis and hemophilia. Thrombin-activable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like pro-enzyme…
(more)
▼ Disequilibrium between coagulation and fibrinolysis can lead to severe haemostatic disorders such as thrombosis and hemophilia. Thrombin-activable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like pro-enzyme that, once activated, attenuates fibrinolysis. TAFI may also mediate connections between coagulation and inflammation. Studies have associated high plasma TAFI levels with risk for thrombotic diseases. Interestingly, steroid hormones, such as estrogen and progestogens used in hormone replacement therapy or oral contraceptive preparations, have been shown to affect plasma TAFI levels. Regulation of the expression of the gene encoding TAFI, CBP2, is likely an important determinant of the role of the TAFI pathway in vivo; this concept motivated the investigations described in this thesis.
In Chapter 2, the results of my research lead to the identification of key transcription factors regulating CPB2. Specifically, we described the binding of NF-Y and HNF-1 to the CPB2 promoter. NF-Y was shown to be an important factor for the basal CPB2 promoter activity. Binding of HNF-1 is essential for the activity of the promoter and is potentially responsible for the liver specific expression of CPB2.
In Chapter 3, we set to investigate the effect of female sex hormone on hepatic expression of CPB2. We demonstrated that the levels of TAFI protein secreted from cultured hepatoma cells (HepG2) are decreased by 17beta-estradiol and progesterone. The change in protein expression was paralleled by decreases in CPB2 mRNA abundance and promoter activity. Deletion analysis of the CPB2 promoter indicated that the genomic effects of estrogen and progesterone are likely mediated via a non-classical mechanism.
In Chapter 4, we evaluated the effects of various inflammatory mediators on expression of the gene encoding mouse TAFI (Cpb2). Our results showed that Cpb2 mRNA abundance and promoter activity are up-regulated by inflammatory mediators IL-1beta, IL-6, and TNFalpha. We also showed that TNFalpha mediates its effect via the binding of NFkB. Additionally, our results suggest that TNFalpha promotes the binding of NFkB to the promoter by increasing its translocation to the nucleus. The NFkB site is not conserved between human and mouse and may explained the different responses to inflammation observed in vivo.
Subjects/Keywords: Gene
;
Regulation
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Garand, M. (2010). Regulation of the Gene Encoding Thrombin-Activable Fibrinolysis Inhibitor
. (Thesis). Queens University. Retrieved from http://hdl.handle.net/1974/5522
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):
Garand, Mathieu. “Regulation of the Gene Encoding Thrombin-Activable Fibrinolysis Inhibitor
.” 2010. Thesis, Queens University. Accessed March 01, 2021.
http://hdl.handle.net/1974/5522.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Garand, Mathieu. “Regulation of the Gene Encoding Thrombin-Activable Fibrinolysis Inhibitor
.” 2010. Web. 01 Mar 2021.
Vancouver:
Garand M. Regulation of the Gene Encoding Thrombin-Activable Fibrinolysis Inhibitor
. [Internet] [Thesis]. Queens University; 2010. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/1974/5522.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Garand M. Regulation of the Gene Encoding Thrombin-Activable Fibrinolysis Inhibitor
. [Thesis]. Queens University; 2010. Available from: http://hdl.handle.net/1974/5522
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Vanderbilt University
20.
-7752-6671.
Predicting gene regulatory changes across human evolution using ancient DNA.
Degree: PhD, Human Genetics, 2020, Vanderbilt University
URL: http://hdl.handle.net/1803/15938
► Sequencing DNA derived from ancient bones (‘aDNA’) enabled direct genetic comparison of anatomically modern humans (AMHs) and their ancestral populations, as well as archaic hominins…
(more)
▼ Sequencing DNA derived from ancient bones (‘aDNA’) enabled direct genetic comparison of anatomically modern humans (AMHs) and their ancestral populations, as well as archaic hominins like Neanderthals and Denisovans. From this, we know that archaic hominins interbred with ancient AMHs, and have a more detailed understanding of population movements throughout history. However, interpreting what genetic differences between groups imply about phenotypic differences remains challenging. To do this, we adapted an approach for imputing
gene regulatory differences based on individuals’ genotypes for application in the context of ancient DNA.
First, to potential
gene regulatory implications of Neanderthal introgression into ancient AMHs, we applied this approach to high-quality genomes from archaic hominins. We found 766 genes that are likely to have been divergently regulated (DR) by Neanderthal haplotypes that do not remain in AMH populations. DR genes include many involved in skeletal phenotypes known to differ between Neanderthals and AMHs, and are also enriched for genes associated with spontaneous abortion, polycystic ovary syndrome, myocardial infarction and melanoma. Comparing DR genes between two Neanderthals and a Denisovan revealed divergence in the immune system and in genes associated with skeletal and dental morphology that are consistent with the archaeological record.
However, to apply a similar approach to more recent evolutionary questions about AMH populations, we needed to consider the fact that most aDNA genomic information is low-coverage, which would impact the ability of our approach to make accurate
gene regulatory predictions. We therefore used simulated genomes and populations to better understand how
gene regulatory models behave with aDNA-derived data, and to develop new approaches to increase their robustness to incomplete data. We found that, while prediction accuracy decreased as the missingness in genomes increased, this effect could be minimized by training models specifically using variants that were reliably captured in the genome data.
Using the knowledge gained from the simulations, we then applied targeted
gene regulatory models to 490 ancient Eurasians to study differences in populations with differing lifestyles. We identified thousands of genes with significant regulatory differences among the three groups. Our results recapitulated known instances of altered
gene expression relevant to population changes diet and lifestyles, such as FADS1, and they also suggested explanations for previously observed signals of selection on LEPR. In general, genes involved in metabolic and immune pathways were the most enriched among these genes, indicating that these pathways are the most likely to have been affected by altered
gene regulation during recent human evolution.
This work provides an avenue for exploring phenotypic differences between ancient groups from genomic information alone, and demonstrates its use in connecting genomic differences to phenotypic differences.
Advisors/Committee Members: Capra, John A (advisor), Cox, Nancy J (advisor).
Subjects/Keywords: gene regulation; ancient DNA
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
-7752-6671. (2020). Predicting gene regulatory changes across human evolution using ancient DNA. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/15938
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Chicago Manual of Style (16th Edition):
-7752-6671. “Predicting gene regulatory changes across human evolution using ancient DNA.” 2020. Doctoral Dissertation, Vanderbilt University. Accessed March 01, 2021.
http://hdl.handle.net/1803/15938.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
MLA Handbook (7th Edition):
-7752-6671. “Predicting gene regulatory changes across human evolution using ancient DNA.” 2020. Web. 01 Mar 2021.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Vancouver:
-7752-6671. Predicting gene regulatory changes across human evolution using ancient DNA. [Internet] [Doctoral dissertation]. Vanderbilt University; 2020. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/1803/15938.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Council of Science Editors:
-7752-6671. Predicting gene regulatory changes across human evolution using ancient DNA. [Doctoral Dissertation]. Vanderbilt University; 2020. Available from: http://hdl.handle.net/1803/15938
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

McMaster University
21.
Mulholland, Emma.
Examining Ribonucleases and G-quadruplex Binding Proteins as Regulators of Gene Expression in S. venezuelae.
Degree: MSc, 2020, McMaster University
URL: http://hdl.handle.net/11375/25812
► Controlling when genes are expressed is critical for the growth of an organism. Studying gene expression regulation in Streptomyces presents an opportunity to better understand…
(more)
▼ Controlling when genes are expressed is critical for the growth of an organism. Studying gene expression regulation in Streptomyces presents an opportunity to better understand how these complex bacteria develop and how they control their impressive biosynthetic capabilities. In this work we investigated the potential role of a G-quadruplex binding protein, and two ribonucleases (RNases) in regulating gene expression in Streptomyces venezuelae. G-quadruplexes are structures that form in DNA or RNA molecules. Depending on their location in DNA, G-quadruplexes can increase or decrease the expression of nearby genes and the stability of a G-quadruplex structure can be affected by G-quadruplex binding proteins. We probed the ability of a G-quadruplex-associated protein from S. venezuelae, TrmB (a tRNA-methyltransferase), to bind and methylate G-quadruplexes and prevent the formation of these structures. We were unable to conclude that TrmB bound or methylated G-quadruplex structures or motifs. RNases are enzymes that cleave RNA molecules and have important roles in controlling cellular RNA levels, and thus gene expression. We investigated the roles of RNase J and RNase III in S. venezuelae. Both of these RNases impact development and specialized metabolism in Streptomyces. We found that the RNase J mutant was unable to grow properly on classical medium containing glycerol. We also documented small RNA fragments that were unique to the RNase J mutant and sought to identify them. To better understand the RNase J and RNase III strains, we conducted RNA-sequencing of wild type S. venezuelae and mutant strains lacking RNase III or RNase J. Comparisons between each mutant and the wild type strain revealed significant changes in genes related to nitrogen assimilation, phosphate uptake, and specialized metabolite production in both the RNase III and RNase J mutant. Together these results contribute to our understanding of the diverse regulatory features that exist in S. venezuelae.
Thesis
Master of Science (MSc)
Studying how gene expression is regulated in the Gram-positive, soil-dwelling bacteria Streptomyces presents an opportunity to better understand how these complex organisms develop and how they control their impressive biosynthetic capabilities. This study investigated the potential role of a G-quadruplex binding protein, and two ribonucleases (RNases) in regulating gene expression in Streptomyces venezuelae. We probed the ability of a G-quadruplex associated protein from S. venezuelae, TrmB, to bind, methylate, and prevent the formation of G-quadruplex structures in DNA. We also investigated the roles of RNase J and RNase III in S. venezuelae growth and development. In RNase J and RNase III mutants, RNA-sequencing revealed dramatic changes in the transcript levels of genes related to phosphate uptake, nitrogen assimilation, and specialized metabolite production. Together these results contribute to our understanding of the diverse and complex regulatory features that exist in S. venezuelae.
Advisors/Committee Members: Elliot, Marie, Biology.
Subjects/Keywords: Microbiology; Gene Regulation; Molecular Genetics
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Mulholland, E. (2020). Examining Ribonucleases and G-quadruplex Binding Proteins as Regulators of Gene Expression in S. venezuelae. (Masters Thesis). McMaster University. Retrieved from http://hdl.handle.net/11375/25812
Chicago Manual of Style (16th Edition):
Mulholland, Emma. “Examining Ribonucleases and G-quadruplex Binding Proteins as Regulators of Gene Expression in S. venezuelae.” 2020. Masters Thesis, McMaster University. Accessed March 01, 2021.
http://hdl.handle.net/11375/25812.
MLA Handbook (7th Edition):
Mulholland, Emma. “Examining Ribonucleases and G-quadruplex Binding Proteins as Regulators of Gene Expression in S. venezuelae.” 2020. Web. 01 Mar 2021.
Vancouver:
Mulholland E. Examining Ribonucleases and G-quadruplex Binding Proteins as Regulators of Gene Expression in S. venezuelae. [Internet] [Masters thesis]. McMaster University; 2020. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/11375/25812.
Council of Science Editors:
Mulholland E. Examining Ribonucleases and G-quadruplex Binding Proteins as Regulators of Gene Expression in S. venezuelae. [Masters Thesis]. McMaster University; 2020. Available from: http://hdl.handle.net/11375/25812

Virginia Tech
22.
Kadelka, Claus Thomas.
Robustness Analysis of Gene Regulatory Networks.
Degree: PhD, Mathematics, 2015, Virginia Tech
URL: http://hdl.handle.net/10919/73302
► Cells generally manage to maintain stable phenotypes in the face of widely varying environmental conditions. This fact is particularly surprising since the key step of…
(more)
▼ Cells generally manage to maintain stable phenotypes in the face of widely varying environmental conditions. This fact is particularly surprising since the key step of
gene expression is fundamentally a stochastic process. Many hypotheses have been suggested to explain this robustness. First, the special topology of
gene regulatory networks (GRNs) seems to be an important factor as they possess feedforward loops and certain other topological features much more frequently than expected. Second, genes often regulate each other in a canalizing fashion: there exists a dominance order amidst the regulators of a
gene, which in silico leads to very robust phenotypes. Lastly, an entirely novel
gene regulatory mechanism, discovered and studied during the last two decades, which is believed to play an important role in cancer, is shedding some light on how canalization may in fact take place as part of a cell’s
gene regulatory program. Short segments of single-stranded RNA, so-called microRNAs, which are embedded in several different types of feedforward loops, help smooth out noise and generate canalizing effects in
gene regulation by overriding the effect of certain genes on others.
Boolean networks and their multi-state extensions have been successfully used to model GRNs for many years. In this dissertation, GRNs are represented in the time- and statediscrete framework of Stochastic Discrete Dynamical Systems (SDDS), which captures the cell-inherent stochasticity. Each
gene has finitely many different concentration levels and its concentration at the next time step is determined by a
gene-specific update rule that depends on the current concentration of the gene’s regulators. The update rules in published
gene regulatory networks are often nested canalizing functions. In Chapter 2, this class of functions is introduced, generalized and analyzed with respect to its potential to confer robustness. Chapter 3 describes a simulation study, which supports the hypothesis that microRNA-mediated feedforward loops have a stabilizing effect on GRNs. Chapter 4 focuses on the cellular DNA mismatch repair machinery. A first regulatory network for this machinery is introduced, partly validated and analyzed with regard to the role of microRNAs and certain genes in conferring robustness to this particular network. Due to steady exposure to mutations, GRNs have evolved over time into their current form. In Chapter 5, a new framework for modeling the evolution of GRNs is developed and then used to identify topological features that seem to stabilize GRNs on an evolutionary time-scale. Chapter 6 addresses a completely separate project in Bioinformatics. A novel functional enrichment method is developed and compared to various popular methods.
Funding for this work was provided by NSF grant CMMI-0908201 and NSF grant 1062878.
Advisors/Committee Members: Laubenbacher, Reinhard C. (committeechair), Herdman, Terry L. (committee member), Murali, T. M. (committee member), Ciupe, Mihaela Stanca (committee member).
Subjects/Keywords: Boolean network; gene regulation; stability
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kadelka, C. T. (2015). Robustness Analysis of Gene Regulatory Networks. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/73302
Chicago Manual of Style (16th Edition):
Kadelka, Claus Thomas. “Robustness Analysis of Gene Regulatory Networks.” 2015. Doctoral Dissertation, Virginia Tech. Accessed March 01, 2021.
http://hdl.handle.net/10919/73302.
MLA Handbook (7th Edition):
Kadelka, Claus Thomas. “Robustness Analysis of Gene Regulatory Networks.” 2015. Web. 01 Mar 2021.
Vancouver:
Kadelka CT. Robustness Analysis of Gene Regulatory Networks. [Internet] [Doctoral dissertation]. Virginia Tech; 2015. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/10919/73302.
Council of Science Editors:
Kadelka CT. Robustness Analysis of Gene Regulatory Networks. [Doctoral Dissertation]. Virginia Tech; 2015. Available from: http://hdl.handle.net/10919/73302

University of Sydney
23.
Szyszka, Taylor Nicole.
Structural Studies of Bromodomain and Extra-Terminal Domain Protein BRD3
.
Degree: 2019, University of Sydney
URL: http://hdl.handle.net/2123/20221
► The work presented in this Thesis examines aspects of the molecular mechanisms underlying gene regulation, focusing on the bromodomain and extra-terminal domain (BET) protein family.…
(more)
▼ The work presented in this Thesis examines aspects of the molecular mechanisms underlying gene regulation, focusing on the bromodomain and extra-terminal domain (BET) protein family. BET proteins use their tandem bromodomains to bind acetylated lysines, such as those present on histones or transcription factors, while the extra-terminal (ET) domain has been described as a putative protein:protein interaction domain. This Thesis aims to connect these two functions, one in the recognition of post-translational modifications relevant to transcriptional activity and the other the recruitment of transcriptional machinery to specific sites in the genome. What emerges is a model wherein the bromodomains and ET domain work in synchrony to carry out various BET protein functions, both in normal and disease pathways. Additionally, the potential of the BET proteins to associate with themselves, each other, and other potential partners is addressed. Overall, this work provides another component to the emerging story of the complex molecular choreography underlying gene regulation.
Subjects/Keywords: NMR;
Protein;
Structure;
Gene Regulation
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MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Szyszka, T. N. (2019). Structural Studies of Bromodomain and Extra-Terminal Domain Protein BRD3
. (Thesis). University of Sydney. Retrieved from http://hdl.handle.net/2123/20221
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):
Szyszka, Taylor Nicole. “Structural Studies of Bromodomain and Extra-Terminal Domain Protein BRD3
.” 2019. Thesis, University of Sydney. Accessed March 01, 2021.
http://hdl.handle.net/2123/20221.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Szyszka, Taylor Nicole. “Structural Studies of Bromodomain and Extra-Terminal Domain Protein BRD3
.” 2019. Web. 01 Mar 2021.
Vancouver:
Szyszka TN. Structural Studies of Bromodomain and Extra-Terminal Domain Protein BRD3
. [Internet] [Thesis]. University of Sydney; 2019. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/2123/20221.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Szyszka TN. Structural Studies of Bromodomain and Extra-Terminal Domain Protein BRD3
. [Thesis]. University of Sydney; 2019. Available from: http://hdl.handle.net/2123/20221
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Texas – Austin
24.
-1259-2181.
Gene regulatory evolution and the origin of complex behaviors in the prairie vole, Microtus ochrogaster.
Degree: PhD, Ecology, Evolution, and Behavior, 2016, University of Texas – Austin
URL: http://hdl.handle.net/2152/46829
► Understanding variation in form and behavior within and among species requires mapping genotypes to phenotypes. Much of this variation depends on differences in regulatory DNA…
(more)
▼ Understanding variation in form and behavior within and among species requires mapping genotypes to phenotypes. Much of this variation depends on differences in regulatory DNA scattered throughout the genome; in the context of behavior, these regulatory sequences govern
gene expression in regions of the brain that shape behavior. Surprisingly few studies have characterized the regulatory changes that underlie the adaptive evolution of brain and behavior. In my PhD dissertation project, I investigated the adaptive role of
gene regulation in the evolution of pair-bonding and sexual fidelity in the prairie voles, Microtus ochrogaster. Expression of Avpr1a in the ventral pallidum plays a critical role in the origin and evolution of pair-bonding in these monogamous voles. In Chapter 1, I have applied phylogenetic and population genetic methods to find signatures of selection in functional elements in the prairie vole genome. I identified a regulatory element of the Avpr1a locus that is under positive selection, this sequence coincides with the origins of expression of this
gene in a reward region, the ventral pallidum. Then, I tested its causality using transgenic mouse enhancer assays. I found that transgenic mice expressing a reporter under the control of this prairie vole enhancer were able to drive expression in the ventral pallidum, but expression was sensitive to insertion site. Interestingly, this
gene also shows profound differences between individuals. In Chapter 2, I applied population genomic tools to demonstrate that this locus shows signatures of balancing selection in a polymorphic enhancer that predicts expression in a spatial memory circuit. I found that alleles that predict aspects of space use and sexual fidelity are strongly linked to each other. Moreover, I show evidence that the evolution of this regulatory element seems to be mediated by a mix of balancing, epistatic and density-dependent selection. In Chapter 3, I performed RNA-sequencing experiments to analyze monogamy-related genomic changes in the brain. I found massive changes in
gene expression of prairie voles in contrast to promiscuous meadow voles, despite their
gene expression modules are very well preserved. Moreover, neuroplasticity –a neural process involved with learning— was strongly activated in prairie but not it meadow vole brains. Overall, the results of these experiments reveal the potential for
gene regulation to drive the adaptive evolution of complex behaviors.
Advisors/Committee Members: Phelps, Steven Michael, 1970- (advisor), Hofmann, Johan (committee member), Matz, Mikhail V (committee member), Atkinson, Nigel S (committee member), Juenger, Thomas E (committee member).
Subjects/Keywords: Behavior; Evolution; Gene; Regulation
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
-1259-2181. (2016). Gene regulatory evolution and the origin of complex behaviors in the prairie vole, Microtus ochrogaster. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/46829
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Chicago Manual of Style (16th Edition):
-1259-2181. “Gene regulatory evolution and the origin of complex behaviors in the prairie vole, Microtus ochrogaster.” 2016. Doctoral Dissertation, University of Texas – Austin. Accessed March 01, 2021.
http://hdl.handle.net/2152/46829.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
MLA Handbook (7th Edition):
-1259-2181. “Gene regulatory evolution and the origin of complex behaviors in the prairie vole, Microtus ochrogaster.” 2016. Web. 01 Mar 2021.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Vancouver:
-1259-2181. Gene regulatory evolution and the origin of complex behaviors in the prairie vole, Microtus ochrogaster. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2016. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/2152/46829.
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete
Council of Science Editors:
-1259-2181. Gene regulatory evolution and the origin of complex behaviors in the prairie vole, Microtus ochrogaster. [Doctoral Dissertation]. University of Texas – Austin; 2016. Available from: http://hdl.handle.net/2152/46829
Note: this citation may be lacking information needed for this citation format:
Author name may be incomplete

The Ohio State University
25.
Belyaevskaya, Anna V.
Characterization of T box riboswitch gene regulation in the
phylum Actinobacteria.
Degree: PhD, Molecular, Cellular and Developmental
Biology, 2015, The Ohio State University
URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1437725058
► Riboswitches are cis-acting RNA regulatory elements located in the 5' untranslated region of a gene. These elements modulate gene expression by structural rearrangements in response…
(more)
▼ Riboswitches are cis-acting RNA regulatory elements
located in the 5' untranslated region of a
gene. These elements
modulate
gene expression by structural rearrangements in response
to an array of physiological signals. T box riboswitches regulate
expression of amino acid-related genes by responding to the
aminoacylation status of a specific tRNA that matches the amino
acid identity of the regulated
gene. Most T box RNAs function at
the level of transcription attenuation. A terminator that prevents
transcription of the downstream
gene forms when aminoacylation of
the cognate tRNA is high, whereas uncharged tRNA promotes
stabilization of an antiterminator that prevents termination and
therefore increases
gene expression. T box riboswitches are
typically composed of three conserved helical domains, designated
Stem I, II, III, the Stem IIA/B pseudoknot, and the competing
terminator and antiterminator elements; these domains include
conserved primary sequence and several secondary structure
elements. However, the predicted structure of many T box
riboswitches from the phylum Actinobacteria differ from those found
in other phyla.A major goal of this research was to characterize
the unusual T box RNAs found in Actinobacteria. These riboswitches
are present in ileS genes, and were divided into three groups based
on the arrangement of the Stem I domain: canonical Stem I;
Ultrashort Stem I (US); and Unusually Structured Stem I Region
(USSR). The US and USSR domains lack conserved elements in the
canonical Stem I that were previously thought to be essential for T
box riboswitch
regulation. In addition, most of T box riboswitches
in Actinobacteria are predicted to regulate
gene expression at the
level of translation initiation instead of transcription
attenuation. In the current study, we demonstrated that several T
box RNAs from Actinobacteria are functional in vitro and undergo
structural rearrangements and changes in ribosomal binding in
response to uncharged tRNAIle that are consistent with
regulation
at the level of translation initiation. Results from fluorescence
assays demonstrated that the US domain binds the cognate tRNAIle in
the absence of other riboswitch sequences, and nuclear magnetic
resonance spectroscopy revealed structural rearrangements in this
unusual domain in response to interaction with the anticodon
stem-loop of the cognate tRNAIle. The US riboswitch variant also
was used to identify a novel tRNA interaction site between the
conserved nts of the Loop E motif in the Stem II domain and the T
arm of the tRNA. This work has investigated the molecular details
of T box riboswitch
gene regulation, explored the codon-anticodon
interaction in the context of unusual RNA structures, and
identified tRNA elements important for tRNA noncanonical role in
gene regulation. Overall, the obtained information increased our
understanding of RNA as a regulatory element.
Advisors/Committee Members: Henkin, Tina (Advisor).
Subjects/Keywords: Microbiology; Riboswitch, Gene Regulation, Actinobacteria
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Belyaevskaya, A. V. (2015). Characterization of T box riboswitch gene regulation in the
phylum Actinobacteria. (Doctoral Dissertation). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1437725058
Chicago Manual of Style (16th Edition):
Belyaevskaya, Anna V. “Characterization of T box riboswitch gene regulation in the
phylum Actinobacteria.” 2015. Doctoral Dissertation, The Ohio State University. Accessed March 01, 2021.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1437725058.
MLA Handbook (7th Edition):
Belyaevskaya, Anna V. “Characterization of T box riboswitch gene regulation in the
phylum Actinobacteria.” 2015. Web. 01 Mar 2021.
Vancouver:
Belyaevskaya AV. Characterization of T box riboswitch gene regulation in the
phylum Actinobacteria. [Internet] [Doctoral dissertation]. The Ohio State University; 2015. [cited 2021 Mar 01].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1437725058.
Council of Science Editors:
Belyaevskaya AV. Characterization of T box riboswitch gene regulation in the
phylum Actinobacteria. [Doctoral Dissertation]. The Ohio State University; 2015. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1437725058

King Abdullah University of Science and Technology
26.
Alkhaldi, Faisal.
An Unexplored Genome Insulating Mechanism in Caenorhabditis Elegans.
Degree: Biological and Environmental Sciences and Engineering (BESE) Division, 2020, King Abdullah University of Science and Technology
URL: http://hdl.handle.net/10754/666047
► Caenorhabditis Elegans genome maintains active H3K36me3 chromatin domains interspersed with repressive H3K27me3 domains on the autosomes’ distal ends. The mechanisms stabilizing these domains and the…
(more)
▼ Caenorhabditis Elegans genome maintains active H3K36me3 chromatin domains interspersed with repressive H3K27me3 domains on the autosomes’ distal ends. The mechanisms stabilizing these domains and the prevention of position-effect variegation remains unknown as no insulator elements have been identified in C. elegans. De-novo motif discovery applied on mes-4 binding sites links the H3K36me3-specific methyltransferase to a class of non-coding DNA known as Periodic An/Tn Clusters (PATCs). PATCs display characteristics of insulator elements such as local nucleosome depletion and their restriction to genes with specific expression profiles and chromatin marks. Finally, I describe a set of experiments to further investigate the role of PATCs and mes-4 in the maintenance of stable chromatin domains using a synthetic biology approach.
Advisors/Committee Members: Frøkjær-Jensen, Christian (advisor), Krattinger, Simon G. (committee member), Tegner, Jesper (committee member).
Subjects/Keywords: Gene Regulation; Insulator elements; Bioinformatics
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Alkhaldi, F. (2020). An Unexplored Genome Insulating Mechanism in Caenorhabditis Elegans. (Thesis). King Abdullah University of Science and Technology. Retrieved from http://hdl.handle.net/10754/666047
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):
Alkhaldi, Faisal. “An Unexplored Genome Insulating Mechanism in Caenorhabditis Elegans.” 2020. Thesis, King Abdullah University of Science and Technology. Accessed March 01, 2021.
http://hdl.handle.net/10754/666047.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Alkhaldi, Faisal. “An Unexplored Genome Insulating Mechanism in Caenorhabditis Elegans.” 2020. Web. 01 Mar 2021.
Vancouver:
Alkhaldi F. An Unexplored Genome Insulating Mechanism in Caenorhabditis Elegans. [Internet] [Thesis]. King Abdullah University of Science and Technology; 2020. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/10754/666047.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Alkhaldi F. An Unexplored Genome Insulating Mechanism in Caenorhabditis Elegans. [Thesis]. King Abdullah University of Science and Technology; 2020. Available from: http://hdl.handle.net/10754/666047
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Vanderbilt University
27.
Lind, Abigail Lee.
The Evolution of Secondary Metabolism and Development Regulation in the Fungal Genus Aspergillus.
Degree: MS, Biomedical Informatics, 2014, Vanderbilt University
URL: http://hdl.handle.net/1803/14522
► Filamentous fungi produce diverse secondary metabolites (SMs) essential to their ecology and adaptation. Although each SM is typically produced by only a handful of species,…
(more)
▼ Filamentous fungi produce diverse secondary metabolites (SMs) essential to their ecology and adaptation. Although each SM is typically produced by only a handful of species, SM production is coordinated with developmental changes by a suite of widely conserved transcriptional regulators. Here, I examined the interplay between the taxonomic narrowness of SM distribution and the broad conservation of global SM and development regulators in four Aspergillus species that include the human pathogen Aspergillus fumigatus and the model organism A. nidulans, producers of medically important SMs including penicillin and gliotoxin. Evolutionary analysis of SM pathways in these four species showed that they are highly divergent, due to changes in both the genomic layout and
gene content of SM pathways. RNA sequencing of two transcriptional regulators of SM and development, veA and mtfA, showed that the effects of deletion of each
gene on SM pathway
regulation were similar in the two species, though the genes and pathways regulated in each species differed. In contrast, the role of these two regulators in development is strikingly different. Whereas veA regulates developmental processes in both species, mtfA regulates development in the self-fertilizing A. nidulans but not in the outcrossing A. fumigatus, despite near total conservation of developmental genes. These results suggest that fungal species have extensively rewired global transcriptional regulators to fit their diverse ecological needs and regulate the rapidly evolving process of secondary metabolite production.
Advisors/Committee Members: John Capra (committee member), John Capra (committee member), Patrick Abbot (committee member), Patrick Abbot (committee member), Antonis Rokas (Committee Chair), Antonis Rokas (Committee Chair).
Subjects/Keywords: gene regulation; evolution; evolution; aspergillus; aspergillus; gene regulation
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lind, A. L. (2014). The Evolution of Secondary Metabolism and Development Regulation in the Fungal Genus Aspergillus. (Thesis). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14522
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):
Lind, Abigail Lee. “The Evolution of Secondary Metabolism and Development Regulation in the Fungal Genus Aspergillus.” 2014. Thesis, Vanderbilt University. Accessed March 01, 2021.
http://hdl.handle.net/1803/14522.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lind, Abigail Lee. “The Evolution of Secondary Metabolism and Development Regulation in the Fungal Genus Aspergillus.” 2014. Web. 01 Mar 2021.
Vancouver:
Lind AL. The Evolution of Secondary Metabolism and Development Regulation in the Fungal Genus Aspergillus. [Internet] [Thesis]. Vanderbilt University; 2014. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/1803/14522.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lind AL. The Evolution of Secondary Metabolism and Development Regulation in the Fungal Genus Aspergillus. [Thesis]. Vanderbilt University; 2014. Available from: http://hdl.handle.net/1803/14522
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Massey University
28.
Yang, Tian.
Development of a tetracycline-inducible lentiviral vector with an instant regulatory system.
Degree: MSc, Biochemistry, 2013, Massey University
URL: http://hdl.handle.net/10179/4319
► Lentiviral vectors, originally derived from human immunodeficiency virus, provide highly efficient viral gene delivery vehicles. Lentiviral vectors often use a constitutive promoter to drive the…
(more)
▼ Lentiviral vectors, originally derived from human immunodeficiency virus, provide highly efficient viral gene delivery vehicles. Lentiviral vectors often use a constitutive promoter to drive the expression of a therapeutic gene. To regulate the expression of a therapeutic gene, a regulatory system such as Tet-On needs to be established in the target cell lines to produce a regulatory protein, reverse Tet-responsive transcriptional activator (rtTA). The expressed rtTA binds to the tetracycline responsive element (TRE) in the promoter in response to doxycycline and activates transcription of gene of interest. A hypothesis in this study is based on the speculation that a basal leaky expression of rtTA in the bi-directional TRE vectors allows instantly inducible expression of a gene of interest and thereby avoids the time-consuming procedures for generating Tet-On cell lines. Based on this hypothesis, a novel lentiviral vector has been developed to examine an instant induction of PP2Cβ as a target gene. Three instantly inducible bicistronic lentiviral vectors [pLenti-Bi-TRE-Tet-on (V), pLenti-Bi-TRE-Tet-on-PP2Cβ WT (WT), pLenti- Bi-TRE-Tet-on-PP2Cβ MUT (MUT)] were constructed and characterised to assess the usefulness of these vectors. Transient transfection of both WT and MUT vectors into HEK293T cells showed a great induction of PP2Cβ expression upon 24 h of 1 μM doxycycline treatment. The result promises the use of these vectors as a mammalian expression plasmid with a feature of inducible target gene expression. However, viral infection studies involving lentiviral packaging and infection procedures did not show a reproducible expression of rtTA or PP2Cβ in HEK293T cells. Therefore, the inducibility of viral transduction needs to be improved for the future studies of PP2Cβ in primary cells.
Subjects/Keywords: Lentiviral vectors;
Gene therapy;
Gene expression;
Gene regulation;
Tetracycline;
Genetic vectors
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Yang, T. (2013). Development of a tetracycline-inducible lentiviral vector with an instant regulatory system. (Masters Thesis). Massey University. Retrieved from http://hdl.handle.net/10179/4319
Chicago Manual of Style (16th Edition):
Yang, Tian. “Development of a tetracycline-inducible lentiviral vector with an instant regulatory system.” 2013. Masters Thesis, Massey University. Accessed March 01, 2021.
http://hdl.handle.net/10179/4319.
MLA Handbook (7th Edition):
Yang, Tian. “Development of a tetracycline-inducible lentiviral vector with an instant regulatory system.” 2013. Web. 01 Mar 2021.
Vancouver:
Yang T. Development of a tetracycline-inducible lentiviral vector with an instant regulatory system. [Internet] [Masters thesis]. Massey University; 2013. [cited 2021 Mar 01].
Available from: http://hdl.handle.net/10179/4319.
Council of Science Editors:
Yang T. Development of a tetracycline-inducible lentiviral vector with an instant regulatory system. [Masters Thesis]. Massey University; 2013. Available from: http://hdl.handle.net/10179/4319
29.
大道, 裕.
メダカをモデルとした細胞型特異的遺伝子制御機構に関する研究 : Studies on the mechanisms of cell type-specific gene regulation using medaka as a simple vertebrate.
Degree: 博士(理学), 2015, Konan University / 甲南大学
URL: http://id.nii.ac.jp/1260/00001546/
;
http://dx.doi.org/10.14990/00001546
一つの個体を構成する同じゲノム情報をもつ細胞が,異なる個性を獲得する過程で中心的な役割を果たすのは,細胞によって特異的な遺伝子群を発現するメカニズムである。多くの生物のゲノムDNA配列が解明された現在においても,細胞によって異なる遺伝情報が読み出されるメカニズムは,依然として大きな謎である。近年,遺伝子制御研究のモデル生物として注目され,研究が盛んになってきた生物として,脊椎動物と同じ脊索動物門に属する海産動物のホヤがある。ホヤのオタマジャクシ幼生は,約3000と少数の細胞からなるにも関わらず,脊椎動物と共通のボディープランをもっている。胚発生が体外で進行し,胚が透明ですべての細胞を顕微鏡下で観察することが可能で,個体レベルの遺伝子機能操作も容易である。さらにゲノムサイズが小さく,シス調節配列の発見や解析が容易であるという利点もある。ホヤはモデル脊索動物としてさまざまな利点があるが,その一方で,特殊化する方向へ進化してきた生物であり,脊椎動物とのさまざまな相違点も存在する。ホヤと同様な研究モデルとしての利点をもちながら,脊椎動物に特有の性質も備えたシンプルなモデルとして注目されているのが,ゼブラフィッシュやメダカなどの小型魚類である。とくにメダカは,ゲノムサイズがゼブラフィッシュの半分であり,シス調節領域のゲノムレベルおよび個体レベルの解析に優れた特徴を備えている。 本研究では,メダカを個体レベルで細胞特異的な遺伝子発現制御機構を解析するためのモデル脊椎動物ととらえ,メダカを用いて新奇現象あるいはあらたに発見された分子の普遍性を明らかにすることを目指した。まず,ホヤを用いて発見された,細胞特異的な転写制御が関わる2つの現象について,その普遍性をメダカを用いて調べた。一つは,生殖腺刺激ホルモン放出ホルモン(GnRH)の非生殖現象における新奇役割の可能性である。もう一つの現象は,ホヤ胚を用いて見いだされた背腹軸に沿った遺伝子発現制御と遺伝子配置およびクロマチンレベルの遺伝子発現制御機構である。メダカを用いて,細胞特異的なシス調節領域を同定し,個体レベルでその活性を解析することにより,ホヤでみいだされたこれらの新奇現象が,脊椎動物にもあてはまる普遍的なものであることを示した。さらに,脊椎動物に特異的な細胞の個性化を伴う現象として,網膜における視細胞の多様性形成機構に注目し,メダカを用いた解析を行った。網膜視細胞の個性化に関わる分子機構として,錐体オプシン遺伝子とシス制御領域を共有する2つのmicroRNAを発見し,転写後調節と転写制御が共役することによる,視細胞の個性化に関わる新しい調節メカニズムを提唱した。
平成26年(2014年度)
Subjects/Keywords: gene regulation; development; medaka; photoreceptor; miRNA
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
大道, . (2015). メダカをモデルとした細胞型特異的遺伝子制御機構に関する研究 : Studies on the mechanisms of cell type-specific gene regulation using medaka as a simple vertebrate. (Thesis). Konan University / 甲南大学. Retrieved from http://id.nii.ac.jp/1260/00001546/ ; http://dx.doi.org/10.14990/00001546
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):
大道, 裕. “メダカをモデルとした細胞型特異的遺伝子制御機構に関する研究 : Studies on the mechanisms of cell type-specific gene regulation using medaka as a simple vertebrate.” 2015. Thesis, Konan University / 甲南大学. Accessed March 01, 2021.
http://id.nii.ac.jp/1260/00001546/ ; http://dx.doi.org/10.14990/00001546.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
大道, 裕. “メダカをモデルとした細胞型特異的遺伝子制御機構に関する研究 : Studies on the mechanisms of cell type-specific gene regulation using medaka as a simple vertebrate.” 2015. Web. 01 Mar 2021.
Vancouver:
大道 . メダカをモデルとした細胞型特異的遺伝子制御機構に関する研究 : Studies on the mechanisms of cell type-specific gene regulation using medaka as a simple vertebrate. [Internet] [Thesis]. Konan University / 甲南大学; 2015. [cited 2021 Mar 01].
Available from: http://id.nii.ac.jp/1260/00001546/ ; http://dx.doi.org/10.14990/00001546.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
大道 . メダカをモデルとした細胞型特異的遺伝子制御機構に関する研究 : Studies on the mechanisms of cell type-specific gene regulation using medaka as a simple vertebrate. [Thesis]. Konan University / 甲南大学; 2015. Available from: http://id.nii.ac.jp/1260/00001546/ ; http://dx.doi.org/10.14990/00001546
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of California – Merced
30.
Mahaffey, Christopher M.
Multidrug resistant protein-three gene regulation.
Degree: Quantitative and Systems Biology, 2010, University of California – Merced
URL: http://www.escholarship.org/uc/item/14h425vs
► This dissertation is presented in two sections. Section one recounts my investigations of modulating the multidrug-resistant protein-three (MRP3) levels, by either activating or silencing the…
(more)
▼ This dissertation is presented in two sections. Section one recounts my
investigations of modulating the multidrug-resistant protein-three (MRP3) levels, by
either activating or silencing the transcription factor Nrf2, in normal lung cells and Keap1
wild-type and mutant non-small cell lung carcinoma cell lines (NSCLC). In section two
direct interactions between Nrf2 and the MRP3 promoter were evaluated in NSCLC.
Additionally, the relationships between MRP3 mRNA levels and Keap1, Nrf2, and p53
status were also investigated in cell lines and tumor specimens. Combined, these sections
explore the complex regulation of the MRP3 gene.
Subjects/Keywords: Biology.; Multidrug resistance.; Gene regulation.; MRP3.
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APA (6th Edition):
Mahaffey, C. M. (2010). Multidrug resistant protein-three gene regulation. (Thesis). University of California – Merced. Retrieved from http://www.escholarship.org/uc/item/14h425vs
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):
Mahaffey, Christopher M. “Multidrug resistant protein-three gene regulation.” 2010. Thesis, University of California – Merced. Accessed March 01, 2021.
http://www.escholarship.org/uc/item/14h425vs.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Mahaffey, Christopher M. “Multidrug resistant protein-three gene regulation.” 2010. Web. 01 Mar 2021.
Vancouver:
Mahaffey CM. Multidrug resistant protein-three gene regulation. [Internet] [Thesis]. University of California – Merced; 2010. [cited 2021 Mar 01].
Available from: http://www.escholarship.org/uc/item/14h425vs.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Mahaffey CM. Multidrug resistant protein-three gene regulation. [Thesis]. University of California – Merced; 2010. Available from: http://www.escholarship.org/uc/item/14h425vs
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
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