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Articles 1 - 25 of 25
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Transcriptional And Epigenetic Regulation Of Cerebellar Development And Function, Shahriyar Majidi
Transcriptional And Epigenetic Regulation Of Cerebellar Development And Function, Shahriyar Majidi
Arts & Sciences Electronic Theses and Dissertations
Compensation among paralogous transcription factors (TFs) confers genetic robustness of cellular processes. Despite the prevalence of this phenotypic phenomenon, an in vivo genome-scale understanding of how TFs dynamically respond within the chromatin context to paralog depletion is still lacking. We explore this question in the mammalian brain by studying the highly conserved MEF2 family of TFs, which confer phenotypic robustness for neuronal processes across multiple brain regions. The paralogous TFs MEF2A and MEF2D are strongly co-expressed in granule neurons of the cerebellum, the most abundant neurons in the brain. Employing single and double conditional knockout of MEF2A and MEF2D in …
Effects Of 4-Methylcyclohexanemethanol On Stress Response Pathway Regulators, In Saccharomyces Cerevisiae, Suk Lan Ser
Effects Of 4-Methylcyclohexanemethanol On Stress Response Pathway Regulators, In Saccharomyces Cerevisiae, Suk Lan Ser
Graduate Theses, Dissertations, and Problem Reports
Hydrotropes are small molecules capable of inducing liquid-liquid phase separation by altering the solubility and conformation states of organic compounds that are increasingly becoming important in organizing chemical reactions and regulating complexes. They prevent protein aggregation causing these proteins to form condensates. Mediator, a highly conserved multi-subunit complex, plays an important role in transcription. Med15, a subunit found within the tail domain of the Mediator complex, works with stress-induced transcription factors and is regulated by many kinases, including CDKs and the AMP kinase, Snf1. Living cells respond by changing molecular and cellular pathways when they are exposed to stressful conditions. …
P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response And Alters Cell State In Vivo, Sydney Moyer
P53 Drives A Transcriptional Program That Elicits A Non-Cell-Autonomous Response And Alters Cell State In Vivo, Sydney Moyer
Dissertations & Theses (Open Access)
Cell stress and DNA damage activate the tumor suppressor p53, triggering transcriptional activation of a myriad of target genes. The molecular, morphological, and physiological consequences of this activation remain poorly understood in vivo. We activated a p53 transcriptional program in mice by deletion of Mdm2, a gene which encodes the major p53 inhibitor. By overlaying tissue-specific RNA-sequencing data from pancreas, small intestine, ovary, kidney, and heart with existing p53 ChIP-sequencing, we identified a large repertoire of tissue-specific p53 genes and a common p53 transcriptional signature of seven genes which included Mdm2 but not p21. Global p53 activation …
Probing The Limits Of Singular Gene Expression Through The Activity Of High Representation Odorant Receptor Transgenes, Eugene Lempert
Probing The Limits Of Singular Gene Expression Through The Activity Of High Representation Odorant Receptor Transgenes, Eugene Lempert
Dissertations, Theses, and Capstone Projects
Singular gene expression is a common phenomenon in biology, making its appearance in immunoglobulin selection, protocadherin expression, X chromosome-inactivation, random monoallelic expression, and olfactory receptor choice. Singularity involves an activation and a feedback step. The mechanisms of singular gene choice have some capacity to integrate additional member genes while still maintaining singularity, but will activate an additional member if an earlier choice was incapable of triggering the feedback step. Odorant Receptor (OR) genes are substantially divergent from each other in terms of coding sequence, promoter structure, and genomic locus, all of which plays a role in how many Olfactory Sensory …
Investigating The Dna-Binding Site For Virb, A Key Transcriptional Regulator Of Shigella Virulence Genes, Using An In Vivo Binding Tool, Monika M.A. Karney, Joy A. Mckenna, Natasha Weatherspoon-Griffin, Alexander D. Karabachev, Makensie E. Millar, Eliese A. Potoceck, Helen J. Wing
Investigating The Dna-Binding Site For Virb, A Key Transcriptional Regulator Of Shigella Virulence Genes, Using An In Vivo Binding Tool, Monika M.A. Karney, Joy A. Mckenna, Natasha Weatherspoon-Griffin, Alexander D. Karabachev, Makensie E. Millar, Eliese A. Potoceck, Helen J. Wing
Life Sciences Faculty Research
The transcriptional anti-silencing and DNA-binding protein, VirB, is essential for the virulence of Shigella species and, yet, sequences required for VirB-DNA binding are poorly understood. While a 7-8 bp VirB-binding site has been proposed, it was derived from studies at a single VirB-dependent promoter, icsB. Our previous in vivo studies at a different VirB-dependent promoter, icsP, found that the proposed VirB-binding site was insufficient for regulation. Instead, the required site was found to be organized as a near-perfect inverted repeat separated by a single nucleotide spacer. Thus, the proposed 7-8 bp VirB-binding site needed to be re-evaluated. Here, we engineer …
Premature Rho-Dependent Transcription Termination In Escherichia Coli : Link To Translation And Gene Regulation, Gabriele Baniulyte
Premature Rho-Dependent Transcription Termination In Escherichia Coli : Link To Translation And Gene Regulation, Gabriele Baniulyte
Legacy Theses & Dissertations (2009 - 2024)
Transcription termination factor Rho is an essential protein in Escherichia coli and related bacteria. The primary function of Rho is to clear unproductive RNA polymerases from the DNA template to minimize negative effects associated with uncontrolled transcription. Although most of the Rho termination events are constitutive, premature Rho-mediated termination was observed at 3% of all affected transcripts indicating active regulation of Rho activity. In this work, we investigated the regulatory mechanism behind premature Rho-dependent transcription termination in two unrelated genes: suhB and topAI. We show that in both cases transcription is terminated inside the coding gene as a consequence of …
Mechanism Of Incorporation And Repair Of Uracil At Highly Transcribed Genes In Saccharomyces Cerevisiae, Norah Auma Owiti
Mechanism Of Incorporation And Repair Of Uracil At Highly Transcribed Genes In Saccharomyces Cerevisiae, Norah Auma Owiti
Dissertations & Theses (Open Access)
Recombination and mutagenesis are elevated by high levels of transcription. The correlation between transcription and genome instability is largely explained by the topological and structural changes in DNA and the associated physical obstacles generated by the transcription machinery. However, such explanation does not directly account for the unique types of mutations originating from the non-canonical residues such as uracil, which are also elevated at highly transcribed regions. Apurinic/Apyrimic or Abasic (AP) sites derived from uracil excision, accumulate at a higher rate in actively transcribed regions of the genome in S. cerevisiae and are primarily repaired by base excision repair (BER) …
Influence Of The Pre-Initiation Complex On Mediator Recruitment In Saccharomyces Cerevisiae, Elisabeth Rose Knoll
Influence Of The Pre-Initiation Complex On Mediator Recruitment In Saccharomyces Cerevisiae, Elisabeth Rose Knoll
Legacy Theses & Dissertations (2009 - 2024)
The Mediator complex plays a central, highly conserved role in eukaryotic transcription by RNA Polymerase II (Pol II) by stimulating the cooperative assembly of a pre-initiation complex (PIC) and recruitment of Pol II for gene activation. Mediator recruitment has generally been ascribed to sequence-specific activators engaging subunits from the tail module which in turn function to recruit the middle and head for complete assembly at the UAS. Mediator subunits of the middle and head then bridge the enhancer to connect with the PIC at the core promoter. It is reported that Mediator recruitment at the UAS preferentially occurs at SAGA-dependent, …
The Role Of The Mediator Transcriptional Co-Activator Complex And Promoter Dependence In Ty1 Retrotransposition In Saccharomyces Cerevisiae, Alicia Salinero
The Role Of The Mediator Transcriptional Co-Activator Complex And Promoter Dependence In Ty1 Retrotransposition In Saccharomyces Cerevisiae, Alicia Salinero
Legacy Theses & Dissertations (2009 - 2024)
Retrotransposons are mobile genetic elements that replicate via an RNA intermediary and constitute a significant portion of most eukaryotic genomes. Saccharomyces cerevisiae has been invaluable to retrotransposon research due to the presence of an active retroelement known as Ty1. The mobility of Ty1 is regulated both positively and negatively by numerous host factors, including several subunits of the Mediator transcriptional co-activator complex. The Mediator core complex is organized into genetically and structurally defined head, middle, and tail modules, along with a transiently associated kinase module. We show that with the exception of the kinase module, deletion of non-essential subunits from …
The Role Of Mfd In Stationary-Phase Oxidative Damage Repair In Bacillus Subtilis, Katelyn E. Porter
The Role Of Mfd In Stationary-Phase Oxidative Damage Repair In Bacillus Subtilis, Katelyn E. Porter
UNLV Theses, Dissertations, Professional Papers, and Capstones
Since the 1950’s it has been shown that bacterial cells accumulate mutations even in non- dividing conditions, but how this type of mutation occurs is still highly debated. In Bacillus subtilis, Mfd, a precursor of the nucleotide excision repair (NER) system, mediates the formation of mutations in stationary-phase or non-replicating cells. In growing cells, Mfd recruits repair when RNA polymerase is stalled during transcription; it then recruits proteins from NER to repair damage. Here, we examine the hypothesis that Mfd mediates the formation of mutations by interacting with cellular components that repair reactive oxygen species (ROS), a natural byproduct of …
Genome-Scale Analyses Of Transcription And Transcriptional Regulation In Bacteria, Devon Marie Fitzgerald
Genome-Scale Analyses Of Transcription And Transcriptional Regulation In Bacteria, Devon Marie Fitzgerald
Legacy Theses & Dissertations (2009 - 2024)
The textbook model of bacterial transcription regulation posits that promoters occur immediately upstream of genes and that transcription factors (TFs) modulate transcription through promoter-proximal binding. However, the recent application of unbiased genome-wide approaches, such as ChIP-seq and RNA-seq, has revealed a much more complex picture, including TF binding and transcription initiation occurring in unexpected locations. This dissertation describes the use of deep sequencing-based approaches to evaluate the genome-wide binding of transcription-related proteins and identify locations of transcription initiation. I have assessed the genome-wide binding of three Escherichia coli TFs and an alternative σ factor. Additionally, I have analyzed genome-wide patterns …
Functional Analysis Of The Ovarian Cancer Susceptibility Locus At 9p22.2 Reveals A Transcription Regulatory Network Mediated By Bnc2 In Ovarian Cells, Melissa Buckley
Functional Analysis Of The Ovarian Cancer Susceptibility Locus At 9p22.2 Reveals A Transcription Regulatory Network Mediated By Bnc2 In Ovarian Cells, Melissa Buckley
USF Tampa Graduate Theses and Dissertations
GWAS have identified several chromosomal loci associated with ovarian cancer risk. However, the mechanism underlying these associations remains elusive. We identify candidate functional Single Nucleotide Polymorphisms (SNPs) at the 9p22.2 ovarian cancer susceptibility locus, several of which map to transcriptional regulatory elements active in ovarian cells identified by FAIRE-seq (Formaldehyde assisted isolation of regulatory elements followed by sequencing) and ChIP-seq (Chromatin Immunoprecipitation followed by sequencing) in relevant cell types. Reporter and electrophoretic mobility shift assays (EMSA) determined the extent to which candidate SNPs had allele specific effects. Chromosome conformation capture (3C) reveals a physical association between Basonuclin 2 (BNC2) and …
Chromatin Insulators: Master Regulators Of The Eukaryotic Genome, Todd Andrew Schoborg
Chromatin Insulators: Master Regulators Of The Eukaryotic Genome, Todd Andrew Schoborg
Doctoral Dissertations
Proper organization of the chromatin fiber within the three dimensional space of the eukaryotic nucleus relies on a number of DNA elements and their interacting proteins whose structural and functional consequences exert significant influence on genome behavior. Chromatin insulators are one such example, where it is thought that these elements assist in the formation of higher order chromatin loop structures by mediating long-range contacts between distant sites scattered throughout the genome. Such looping serves a dual role, helping to satisfy both the physical constraints needed to package the linear DNA polymer within the small volume of the nucleus while simultaneously …
Differential Regulation Of White-Opaque Switching By Individual Subunits Of Candida Albicans Mediator, Anda Zhang, Zhongle Liu, Lawrence C. Myers
Differential Regulation Of White-Opaque Switching By Individual Subunits Of Candida Albicans Mediator, Anda Zhang, Zhongle Liu, Lawrence C. Myers
Dartmouth Scholarship
The multisubunit eukaryotic Mediator complex integrates diverse positive and negative gene regulatory signals and transmits them to the core transcription machinery. Mutations in individual subunits within the complex can lead to decreased or increased transcription of certain subsets of genes, which are highly specific to the mutated subunit. Recent studies suggest a role for Mediator in epigenetic silencing. Using white-opaque morphological switching in Candida albicans as a model, we have shown that Mediator is required for the stability of both the epigenetic silenced (white) and active (opaque) states of the bistable transcription circuit driven by the master regulator Wor1. Individual …
Farnesol And Cyclic Amp Signaling Effects On The Hypha-To-Yeast Transition In Candida Albicans, Allia K. Lindsay, Aurélie Deveau, Amy E. Piispanen, Deborah A. Hogan
Farnesol And Cyclic Amp Signaling Effects On The Hypha-To-Yeast Transition In Candida Albicans, Allia K. Lindsay, Aurélie Deveau, Amy E. Piispanen, Deborah A. Hogan
Dartmouth Scholarship
Candida albicans, a fungal pathogen of humans, regulates its morphology in response to many environmental cues and this morphological plasticity contributes to virulence. Farnesol, an autoregulatory molecule produced by C. albicans, inhibits the induction of hyphal growth by inhibiting adenylate cyclase (Cyr1). The role of farnesol and Cyr1 in controlling the maintenance of hyphal growth has been less clear. Here, we demonstrate that preformed hyphae transition to growth as yeast in response to farnesol and that strains with increased cyclic AMP (cAMP) signaling exhibit more resistance to farnesol. Exogenous farnesol did not induce the hypha-to-yeast transition in mutants …
The Role Of Ess1 In Survival, Morphogenetic Switching And Transcription In The Fungal Pathogen Candida Albicans, Dhanushki Poornima Samaranayake
The Role Of Ess1 In Survival, Morphogenetic Switching And Transcription In The Fungal Pathogen Candida Albicans, Dhanushki Poornima Samaranayake
Legacy Theses & Dissertations (2009 - 2024)
Candida albicans is a fungal pathogen that causes serious infections among immune-compromised patients and premature infants. C. albicans can become drug resistant, therefore, identifying new antifungal drug targets is an important goal. Here, we study a peptidyl-prolyl cis/trans isomerase called Ess1 as a potential drug target. Ess1 is conserved among pathogenic fungi, and therefore, potential inhibitors of Ess1 should display a broad spectrum of activity. We confirm that Ess1 is essential for growth in Candida albicans, but unlike the previously published find, deleting one copy of the C. albicans ESS1 gene did not affect morphogenetic switching. However, further reducing activity …
The Role Of Transcription In Stationary Phase Mutagenesis In Bacillus Subtilis, Holly Anne Martin
The Role Of Transcription In Stationary Phase Mutagenesis In Bacillus Subtilis, Holly Anne Martin
UNLV Theses, Dissertations, Professional Papers, and Capstones
Stationary phase mutagenesis, also known as stress-induced or adaptive mutagenesis, is defined as the accumulation of mutations during conditions of no net growth or conditions of stress. This process has been implicated in acquiring antibiotic resistance and evasion of host immune responses in microbial pathogens and in the generation of mutations that lead to neoplasia in animal cells. Previous work has shown that defects in DNA synthesis and repair systems contribute to the formation of adaptive mutations; however the role of transcription in the accumulation of mutations is still being examined. It is speculated that transcriptional derepression leads to an …
The Role Of Ledgf/P75 In Transcriptional Regulation, Jeffrey Ryan Kugelman
The Role Of Ledgf/P75 In Transcriptional Regulation, Jeffrey Ryan Kugelman
Open Access Theses & Dissertations
The Lens Epithelial Derived Growth Factor p75 (LEDGF/p75) is a chromatin bound protein whose cellular function is not yet clearly known. A role in transcriptional regulation had been previously proposed based on its interaction with the basal transcriptional machinery and on its effects on the expression of genes involved in the cellular response to environmental stresses. To further elucidate the function of LEDGF/p75, we conducted a global and unbiased evaluation of the role of this protein in gene expression. To that aim, we performed a microarray analysis of cellular gene expression in cells that are severely depleted of LEDGF/p75. To …
Analysing The Effects Of Loss Of Sin3 In Drosophila Melanogaster, Aishwarya Swaminathan
Analysing The Effects Of Loss Of Sin3 In Drosophila Melanogaster, Aishwarya Swaminathan
Wayne State University Dissertations
Sin3A has been previously shown to be an essential gene for Drosophila viability and is implicated in the regulation of cell cycle. In this study, we show that SIN3 is not only required for embryonic viability but also for post-embryonic development. Genetic analysis suggests that the different isoforms of SIN3 may regulate unique sets of genes during development. The developmental lethality occurring due to ubiquitous knock down of SIN3 is hypothesized to be to the result of defects in cell proliferation. Conditional knock down of SIN3 in the wing discs results in a curly wing phenotype in the adult fly. …
Ovarian Development In Mice Requires The Gata4-Fog2 Transcription Complex, Nikolay L. Manuylov, Fatima O. Smagulova, Lyndsay Leach, Sergei G. Tevosian
Ovarian Development In Mice Requires The Gata4-Fog2 Transcription Complex, Nikolay L. Manuylov, Fatima O. Smagulova, Lyndsay Leach, Sergei G. Tevosian
Dartmouth Scholarship
We have demonstrated previously that mammalian sexual differentiation requires both the GATA4 and FOG2 transcriptional regulators to assemble the functioning testis. Here we have determined that the sexual development of female mice is profoundly affected by the loss of GATA4-FOG2 interaction. We have also identified the Dkk1 gene, which encodes a secreted inhibitor of canonical beta-catenin signaling, as a target of GATA4-FOG2 repression in the developing ovary. The tissue-specific ablation of the beta-catenin gene in the gonads disrupts female development. In Gata4(ki/ki); Dkk1(-/-) or Fog2(-/-); Dkk1(-/-) embryos, the normal ovarian gene expression pattern is partially restored. Control of ovarian development …
Variation In Molybdenum Content Across Broadly Distributed Populations Of Arabidopsis Thaliana Is Controlled By A Mitochondrial Molybdenum Transporter (Mot1), Ivan Baxter, Balasubramaniam Muthukumar, Hyeong Cheol Park, Peter Buchner, Brett Lahner, John Danku, Keyan Zhao, Joohyun Lee, Malcolm J. Hawkesford, Mary Lou Guerinot, David E. Salt
Variation In Molybdenum Content Across Broadly Distributed Populations Of Arabidopsis Thaliana Is Controlled By A Mitochondrial Molybdenum Transporter (Mot1), Ivan Baxter, Balasubramaniam Muthukumar, Hyeong Cheol Park, Peter Buchner, Brett Lahner, John Danku, Keyan Zhao, Joohyun Lee, Malcolm J. Hawkesford, Mary Lou Guerinot, David E. Salt
Dartmouth Scholarship
Molybdenum (Mo) is an essential micronutrient for plants, serving as a cofactor for enzymes involved in nitrate assimilation, sulfite detoxification, abscisic acid biosynthesis, and purine degradation. Here we show that natural variation in shoot Mo content across 92 Arabidopsis thaliana accessions is controlled by variation in a mitochondrially localized transporter (Molybdenum Transporter 1 - MOT1) that belongs to the sulfate transporter superfamily. A deletion in the MOT1 promoter is strongly associated with low shoot Mo, occurring in seven of the accessions with the lowest shoot content of Mo. Consistent with the low Mo phenotype, MOT1 expression in low Mo accessions …
Simpler Mode Of Inheritance Of Transcriptional Variation In Male Drosophila Melanogaster, Marta Wayne, Marina Telonis-Scott, Lisa Bono, Lawrence G. Harshman, Artyom Kopp, Sergey V. Nuzhdin, Lauren Mcintyre
Simpler Mode Of Inheritance Of Transcriptional Variation In Male Drosophila Melanogaster, Marta Wayne, Marina Telonis-Scott, Lisa Bono, Lawrence G. Harshman, Artyom Kopp, Sergey V. Nuzhdin, Lauren Mcintyre
Lawrence G. Harshman Publications
Sexual selection drives faster evolution in males. The X chromosome is potentially an important target for sexual selection, because hemizygosity in males permits accumulation of alleles, causing tradeoffs in fitness between sexes. Hemizygosity of the X could cause fundamentally different modes of inheritance between the sexes, with more additive variation in males and more nonadditive variation in females. Indeed, we find that genetic variation for the transcriptome is primarily additive in males but nonadditive in females. As expected, these differences are more pronounced on the X chromosome than the autosomes, but autosomal loci are also affected, possibly because of X-linked …
A Subset Of Arabidopsis Ap2 Transcription Factors Mediates Cytokinin Responses In Concert With A Two-Component Pathway, Aaron M. Rashotte, Michael G. Mason, Claire E. Hutchison, Fernando J. Ferreira, G. Eric Schaller, Joseph J. Kieber
A Subset Of Arabidopsis Ap2 Transcription Factors Mediates Cytokinin Responses In Concert With A Two-Component Pathway, Aaron M. Rashotte, Michael G. Mason, Claire E. Hutchison, Fernando J. Ferreira, G. Eric Schaller, Joseph J. Kieber
Dartmouth Scholarship
The plant hormone cytokinin regulates numerous growth and developmental processes. A signal transduction pathway for cytokinin has been elucidated that is similar to bacterial two-component phosphorelays. In Arabidopsis, this pathway is comprised of receptors that are similar to sensor histidine kinases, histidine-containing phosphotransfer proteins, and response regulators (ARRs). There are two classes of response regulators, the type-A ARRs, which act as negative regulators of cytokinin responses, and the type-B ARRs, which are transcription factors that play a positive role in mediating cytokinin-regulated gene expression. Here we show that several closely related members of the Arabidopsis AP2 gene family of …
Principal Component Analysis For Predicting Transcription-Factor Binding Motifs From Array-Derived Data, Yunlong Liu, Matthew P Vincenti, Hiroki Yokota
Principal Component Analysis For Predicting Transcription-Factor Binding Motifs From Array-Derived Data, Yunlong Liu, Matthew P Vincenti, Hiroki Yokota
Dartmouth Scholarship
The responses to interleukin 1 (IL-1) in human chondrocytes constitute a complex regulatory mechanism, where multiple transcription factors interact combinatorially to transcription-factor binding motifs (TFBMs). In order to select a critical set of TFBMs from genomic DNA information and an array-derived data, an efficient algorithm to solve a combinatorial optimization problem is required. Although computational approaches based on evolutionary algorithms are commonly employed, an analytical algorithm would be useful to predict TFBMs at nearly no computational cost and evaluate varying modelling conditions. Singular value decomposition (SVD) is a powerful method to derive primary components of a given matrix. Applying SVD …
Cole1 Copy Number Mutants., Londa Schmidt, Joseph Inselburg
Cole1 Copy Number Mutants., Londa Schmidt, Joseph Inselburg
Dartmouth Scholarship
A deletion mutant of the colicin E1-derived plasmid, pDMS6642, exhibited an approximately fourfold increase in copy number. We subsequently isolated hydroxylamine-induced mutants of that plasmid that had a further increase in copy number. Analysis of them suggests that the increased copy number of pDMS6642 is associated with transcriptional readthrough from a Tn3 transposon into the region of ColE1 containing information that influences plasmid replication. The hydroxylamine mutation in one copy number mutant appeared to increase the plasmid copy number by stimulating readthrough transcription from the Tn3 transposon into the ColE1 replication control region, whereas the other hydroxylamine mutation acts by …