Open Access. Powered by Scholars. Published by Universities.®

Molecular Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Theses/Dissertations

Transcription

Discipline
Institution
Publication Year
Publication

Articles 1 - 20 of 20

Full-Text Articles in Molecular Biology

Protein Degradation Regulates Phospholipid Biosynthetic Gene Expression In Saccharomyces Cerevisiae, Bryan Salas-Santiago Jan 2019

Protein Degradation Regulates Phospholipid Biosynthetic Gene Expression In Saccharomyces Cerevisiae, Bryan Salas-Santiago

Doctoral Dissertations

Transcriptional regulation of most phospholipid biosynthetic genes in Saccharomyces cerevisiae is coordinated by inositol and choline. Inositol affects phosphatidic acid (PA) intracellular levels. Opi1p interacts physically with PA and is the main repressor of the phospholipid biosynthetic genes. It is localized in the endoplasmic reticulum (ER) bound to the ER membrane protein Scs2p. When PA levels drop, Opi1p is translocated into the nucleus repressing most phospholipid biosynthetic genes. The OPI1 locus was identified in a screen looking for overproduction and excretion of inositol (Opi-). Opi- mutants are generally associated with a defect in repression of the ...


Effects Of Nicotine On The Cyp6a8 Gene Promoter Of Drosophila Melanogaster, Leslie M. Stroud May 2017

Effects Of Nicotine On The Cyp6a8 Gene Promoter Of Drosophila Melanogaster, Leslie M. Stroud

Chancellor’s Honors Program Projects

No abstract provided.


The Regenerating Fin As A Model To Examine The Skeletal Defects Of Roberts Syndrome, Rajeswari Banerji Jan 2017

The Regenerating Fin As A Model To Examine The Skeletal Defects Of Roberts Syndrome, Rajeswari Banerji

Theses and Dissertations

Roberts Syndrome (RBS) is a human developmental disorder characterized by craniofacial abnormalities, limb malformation and often severe mental retardation. RBS arises from mutations in the cohesin auxiliary factor ESCO2 that targets the SMC3 subunit of the cohesin complex. Mutations in cohesin subunits and a subset of cohesin auxiliary factors gives rise to a related developmental malady termed Cornelia de Lange Syndrome (CdLS). They are collectively termed cohesinopathies since both disorders comprise overlapping phenotypes and the causative genes for both syndromes perform common activities. The underlying cause of CdLS is largely modeled as occurring through transcriptional deregulation. Whereas, the mechanism that ...


Significance Of Pten Phosphorylation And Its Nuclear Function In Lung Cancer, Prerna Malaney Nov 2016

Significance Of Pten Phosphorylation And Its Nuclear Function In Lung Cancer, Prerna Malaney

Graduate Theses and Dissertations

Phosphorylation mediated inactivation of PTEN leads to multiple malignancies with increased severity. However, the consequence of such inactivation on downstream functions of PTEN are poorly understood. Therefore, the objective of my thesis is to ascertain the molecular mechanisms by which PTEN phosphorylation drives lung cancer. PTEN phosphorylation at the C-terminal serine/threonine cluster abrogates its tumor suppressor function. Despite the critical role of the PTEN C-tail in regulating its function, the crystal structure of the C-tail remains unknown. Using bioinformatics and structural analysis, I determined that the PTEN C-tail is an intrinsically disordered region and is a hot spot for ...


Regulation Of Gene Expression By The Mediator Kinase Cdk19, Katherine Audrey Audetat Jan 2016

Regulation Of Gene Expression By The Mediator Kinase Cdk19, Katherine Audrey Audetat

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The Mediator complex is a required co-activator of RNA Polymerase II (Pol II), the enzyme responsible for the transcription of all protein coding genes in eukaryotes. Mediator facilitates transcription factor-dependent gene expression by directly interacting with gene specific transcription factors and Pol II and the general transcription machinery. Mediator consists of up to 29 subunits; a four-subunit “CDK module” reversibly associates with Core-Mediator and alters its structure and activity. Most of the work on the CDK module has been done in yeast, and has focused on the CDK module subunits CDK8, MED12, and MED13. These three subunits have paralog proteins ...


The Mitotic Genome: Accessibility And Transcriptional Control, Chris Hsiung Jan 2016

The Mitotic Genome: Accessibility And Transcriptional Control, Chris Hsiung

Publicly Accessible Penn Dissertations

Mitosis entails dramatic global alterations to genome structure and regulation, including

chromosome condensation, dissociation of the transcriptional machinery from chromosomes, and transcriptional silencing. Here I report studies that address the macromolecular accessibility of the mitotic genome and the control of transcriptional reactivation upon mitotic exit in a mammalian cell line. The results obtained from measuring the sensitivity of chromatin to DNase I cleavage by sequencing (DNase-seq) in pure mitotic cell populations demonstrate that macromolecular accessibility of the mitotic genome is widely preserved. Thus, steric hindrance from chromatin condensation is insufficient for explaining the eviction of transcription factors from mitotic chromatin ...


Hepatic Nutrient And Hormonal Regulation Of The Pancreatic-Derived Factor (Pander) Promoter, Whitney Ratliff Nov 2015

Hepatic Nutrient And Hormonal Regulation Of The Pancreatic-Derived Factor (Pander) Promoter, Whitney Ratliff

Graduate Theses and Dissertations

PANcreatic-DERived factor (PANDER, FAM3B) has been shown to regulate glycemic levels via interactions with both pancreatic islets and the liver. Although PANDER is predominantly expressed from the endocrine pancreas, recent work has provided sufficient evidence that the liver may also be an additional tissue source of PANDER production. At physiological levels, PANDER is capable of disrupting insulin signaling and promoting increased hepatic glucose production. As shown in some animal models, strong expression of PANDER, induced by viral delivery within the liver, induces hepatic steatosis. However, no studies to date have explicitly characterized the transcriptional regulation of PANDER from the liver ...


Functional Analysis Of The Ovarian Cancer Susceptibility Locus At 9p22.2 Reveals A Transcription Regulatory Network Mediated By Bnc2 In Ovarian Cells, Melissa Buckley Jan 2015

Functional Analysis Of The Ovarian Cancer Susceptibility Locus At 9p22.2 Reveals A Transcription Regulatory Network Mediated By Bnc2 In Ovarian Cells, Melissa Buckley

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 ...


Single Human Cells Use Transcriptional Mechanisms To Compensate For Differences In Cell Size And Dna Content, Olivia Padovan-Merhar Jan 2015

Single Human Cells Use Transcriptional Mechanisms To Compensate For Differences In Cell Size And Dna Content, Olivia Padovan-Merhar

Publicly Accessible Penn Dissertations

Human cells are dynamic: they grow, replicate their genetic information (DNA), and divide. Clonal populations of cells can display marked heterogeneity in size, leading to significant variability in the ratio of DNA to cellular volume. Despite this variability, cells must maintain a constant concentration of RNA and protein, produced from DNA, to ensure proper functionality. How do larger cells produce more output from the same amount of DNA? How do cells that have replicated their DNA prior to cellular division produce the same output as before? Using RNA fluorescence in situ hybridization (RNA FISH), we visualize and count individual RNA ...


A Distinct Subunit Composition Of Chromatin-Bound Mediator, Eliza Foster Jan 2015

A Distinct Subunit Composition Of Chromatin-Bound Mediator, Eliza Foster

Undergraduate Honors Theses

Mediator is a multi-subunit protein complex that plays an essential role in transcription by integrating DNA-binding transcription factors (TFs) bound to the enhancer and general transcription factors (GTFs) bound to the promoter of a gene. Mediator is similar to other general transcription factors in that it associates with the promoter region of DNA and interacts with RNA polymerase II (RNAPII), but its large size and many subunits allows it to interact with both GTFs at the promoter and other TFs bound to enhancer DNA. Mediator may regulate transcription by interacting with chromatin. Mediator can exist in different structural states and ...


Regulation Of Saga By The N-Terminus Of Spt7 In Saccharomyces Cerevisiae, Dominik Dobransky Aug 2014

Regulation Of Saga By The N-Terminus Of Spt7 In Saccharomyces Cerevisiae, Dominik Dobransky

Electronic Thesis and Dissertation Repository

Spt7 is a 1,332 residue protein critical for maintaining structural integrity of the SAGA complex. I demonstrated that the extreme N-terminus of Spt7 plays an important role in SAGA function. Deletion of the first 73 (Spt773-1332) and 121 (Spt7121-1332) N- terminal residues resulted in slow growth, decreased transcriptional activation at PHO5 and INO1, and a partial decrease in acetylation at lysine 18 of histone H3 at PHO5. The Spt7121-1332 mutant did not affect Spt7’s association with Gcn5 or Tra1, or its localization within the cell. Mutation of the first four positively charged residues to glutamine ...


Multiple Roles Of Brd4 In The Human Papillomavirus Life Cycle, Christine M. Helfer Jan 2014

Multiple Roles Of Brd4 In The Human Papillomavirus Life Cycle, Christine M. Helfer

Publicly Accessible Penn Dissertations

ABSTRACT

MULTIPLE ROLES OF BRD4 IN THE HUMAN

PAPILLOMAVIRUS LIFE CYCLE

Christine M. Helfer

Jianxin You

While human papillomavirus (HPV) vaccines protect against acquiring new infections, there is currently no antiviral treatment for eradicating persistent HPV infections. In this study, I demonstrated that the cellular chromatin binding protein, Brd4, in association with HPV E2 protein, is important for multiple HPV functions including replication, maintenance of viral genomes, and regulation of viral gene transcription. These studies suggest that the E2–Brd4 complex could be an effective target to disrupt the HPV life cycle. Using bimolecular fluorescence complementation, we demonstrate that E2 ...


Chromatin Insulators: Master Regulators Of The Eukaryotic Genome, Todd Andrew Schoborg Aug 2013

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 ...


Human Adenovirus E1a Binds And Retasks Cellular Hbre1, Blocking Interferon Signalling And Activating Virus Early Gene Transcription, Gregory J. Fonseca Jun 2013

Human Adenovirus E1a Binds And Retasks Cellular Hbre1, Blocking Interferon Signalling And Activating Virus Early Gene Transcription, Gregory J. Fonseca

Electronic Thesis and Dissertation Repository

Upon infection, human adenovirus (HAdV) must block interferon signaling and activate the expression of its early genes to reprogram the cellular environment to support virus replication. During the initial phase of infection, these processes are orchestrated by the first HAdV gene expressed during infection, early region 1A (E1A). E1A binds and appropriates components of the cellular transcriptional machinery to modulate cellular gene transcription and activate viral early genes transcription. We have identified hBre1/RNF20 as a novel target of E1A. hBre1 is an E3 ubiquitin ligase which acts with the Ube2b E2 conjugase and accessory factors RNF40 and WAC1 to ...


Molecular Functions Of Mll Phd3 Binding To Its Ligands Cyp33 And H3k4me3, Gayathree Raman Jan 2013

Molecular Functions Of Mll Phd3 Binding To Its Ligands Cyp33 And H3k4me3, Gayathree Raman

Dissertations

Mixed Lineage Leukemia protein (MLL) is required for proper embryonic development, and hematopoiesis. It is a SET domain containing histone methyl transferase that trimethylates histone H3 on lysine 4 (H3K4Me3), a histone modification that correlates with active transcription. The 3rd PHD finger of MLL binds to H3K4me3. Thus MLL is a "writer" with an embedded "reader" for H3K4Me3. Cyp33 is another known ligand of MLL PHD3. Over expression of Cyp33 results in transcriptional repression of MLL target genes.

The aim of this study is to determine the biological function of MLL PHD3 binding to H3K4Me3 or Cyp33. Cyp33 binding to ...


Epigenomic And Transcriptional Regulation Of Hepatic Metabolism By Rev-Erb And Hdac3, Dan Feng Jan 2013

Epigenomic And Transcriptional Regulation Of Hepatic Metabolism By Rev-Erb And Hdac3, Dan Feng

Publicly Accessible Penn Dissertations

Metabolic activities are regulated by the circadian clock, and disruption of the clock exacerbates metabolic diseases including obesity and diabetes. Transcriptomic studies in metabolic organs suggested that the circadian clock drives the circadian expression of important metabolic genes. Here we show that histone deacetylase 3 (HDAC3) is recruited to the mouse liver genome in a circadian manner. Histone acetylation is inversely related to HDAC3 binding, and this rhythm is lost when HDAC3 is absent. Diurnal recruitment of HDAC3 corresponds to the expression pattern of REV-ERBα, an important component of the circadian clock. REV-ERBα colocalizes with HDAC3 near genes regulating lipid ...


Trim24-Regulated Estrogen Response Is Dependent On Specific Histone Modifications In Breast Cancer Cells, Teresa T. Yiu Dec 2012

Trim24-Regulated Estrogen Response Is Dependent On Specific Histone Modifications In Breast Cancer Cells, Teresa T. Yiu

UT GSBS Dissertations and Theses (Open Access)

In this dissertation, I discovered that function of TRIM24 as a co-activator

of ERα-mediated transcriptional activation is dependent on specific histone

modifications in tumorigenic human breast cancer-derived MCF7 cells. In the first

part, I proved that TRIM24-PHD finger domain, which recognizes unmethylated

histone H3 lysine K4 (H3K4me0), is critical for ERα-regulated transcription.

Therefore, when LSD1-mediated demethylation of H3K4 is inhibited, activation of

TRIM24-regulated ERα target genes is greatly impaired. Importantly, I

demonstrated that TRIM24 and LSD1 are cyclically recruited to estrogen

responsive elements (EREs) in a time-dependent manner upon estrogen

induction, and depletion of their expression exert corresponding time-dependent

effect ...


Prevalence And Physiological Significance Of Gene Looping In Saccharomyces Cerevisiae, Banupriya Mukundan Jan 2012

Prevalence And Physiological Significance Of Gene Looping In Saccharomyces Cerevisiae, Banupriya Mukundan

Wayne State University Dissertations

My Ph.D. dissertation work is focused on studying the role of promoter-bound transcription initiation factors involved in gene looping. In this study we showed that the RNAP II subunit Rpb4 has a significant effect on termination of transcription. Gene looping is disrupted in the absence of Rpb4. Rpb4 shows a strong physical interaction with the Mediator subunit Srb5. Mediator subunit Srb5 crosslinked to the 5' and 3' ends of INO1 and CHA1 genes and is required for proper termination of transcription of these genes. Srb5 affected termination of transcription through its interaction with the CF1 complex. Srb5 interaction with ...


Higher-Order Chromatin Organization In Hematopoietic Transcription, Wulan Deng Jan 2012

Higher-Order Chromatin Organization In Hematopoietic Transcription, Wulan Deng

Publicly Accessible Penn Dissertations

Coordinated transcriptional networks underlie complex developmental processes. Transcription factors play central roles in such networks by binding to core promoters and regulatory elements and thereby controlling transcription activities and chromatin states in the genome. GATA1 is a hematopoietic transcription factor that controls multiple hematopoietic lineages by activating and repressing gene expression, yet the in vivo mechanisms that specify these opposing activities are unknown. By examining the composition of GATA1 associated protein complexes in a genetic complementary erythroid cell system as well as through the use of tiling arrays, we found that a multi-protein complex containing SCL/TAL1, LMO2, Ldb1, and ...


The Role Of Multiple Ccaat-Binding Factors In Candida Albicans Gene Expression, Lashall Lynn Bates Dec 2009

The Role Of Multiple Ccaat-Binding Factors In Candida Albicans Gene Expression, Lashall Lynn Bates

Theses and Dissertations

The CCAAT-binding factor is a heterooligomeric transcription factor that is evolutionarily conserved in eukaryotes. In yeast, the DNA-binding component that interacts with the CCAAT consensus sequence in promoters consists of the subunits termed Hap2p, Hap3p and Hap5p. In yeast and fungi, a fourth subunit, Hap4p, is required for regulating gene expression. The goal of this research is to understand the function of the Candida albicans CCAAT-binding factor and how it relates to virulence and pathogenicity. C. albicans is a human opportunistic pathogen responsible for a variety of mucosal and systemic infections that result in significant morbidity and mortality, particularly in ...