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Epigenetics

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Full-Text Articles in Molecular Biology

The Tale Factors And Nuclear Factor Y Cooperate To Drive Transcription At Zygotic Genome Activation, William J. Stanney Iii Aug 2019

The Tale Factors And Nuclear Factor Y Cooperate To Drive Transcription At Zygotic Genome Activation, William J. Stanney Iii

GSBS Dissertations and Theses

The TALE factors, comprising the pbx and prep/meis gene families, are transcription factors (TFs) vital to the proper formation of anterior anatomical structures during embryonic development. Although best understood as essential cofactors for tissue-specific TFs such as the hox genes during segmentation, the TALE factors also form complexes with nuclear factor Y (NFY) in the early zygote. In zebrafish, Pbx4, Prep1, and NFY are maternally deposited and can access their DNA binding sites in compact chromatin. Our results suggest that TALE/NFY complexes have a unique role in early embryonic development which is distinct from each factor’s independent ...


The Role Of H3k4 Methyltransferases In Drosophila Memory, Nicholas Raun Jan 2019

The Role Of H3k4 Methyltransferases In Drosophila Memory, Nicholas Raun

Electronic Thesis and Dissertation Repository

Gene transcription required for long-term memory requires the modification of histones. However, there are still many uncertainties about the identity and spatial expression of genes regulated by histone modifications during memory related processes. In this project I examined the role of Drosophila melanogaster methyltransferases Set1 and trx in courtship memory. Genetic knockdown of Set1 and trx in the mushroom body (MB) revealed that Set1 was necessary for short- and long-term memory, while trx was only required for long-term memory. Transcriptional profiling of MBs following trx-knockdown revealed expression changes in MB-enriched genes and genes involved in RNA processing. Among the ...


Epigenetic Variation In A Reptile With Temperature-Dependent Sex Determination And Inspiring A Diverse Future For Stem, Daniela Victoria Flores Jan 2019

Epigenetic Variation In A Reptile With Temperature-Dependent Sex Determination And Inspiring A Diverse Future For Stem, Daniela Victoria Flores

Graduate Theses and Dissertations

Vertebrates with temperature-dependent sex determination (TSD), a mechanism that relies on incubation temperature to irreversibly determine the sex of developing embryos, are threatened by ongoing changes in climate and local environmental conditions. Previous studies have suggested that behavioral and molecular plasticity in this system may provide opportunities for these species to adapt to these changes. Although decades of research have uncovered key aspects, a complete molecular mechanism of TSD remains elusive. Epigenetic studies have the potential to unlock crucial information previously cryptic in traditional genetic studies. Recent studies have shown that environmental factors and maternal effects can greatly influence an ...


Genetic And Epigenetic Investigations On Pulmonary Hypertension Syndrome In Meat Type- Chickens, Khaloud Alzahrani Dec 2018

Genetic And Epigenetic Investigations On Pulmonary Hypertension Syndrome In Meat Type- Chickens, Khaloud Alzahrani

Theses and Dissertations

This dissertation presents a collection of studies that investigate the genetic and epigenetic associations to ascites phenotype in broiler chickens. Ascites is a significant metabolic disease associated with fast-growing meat-type chickens (broilers) and is a terminal result of pulmonary hypertension syndrome PHS. It is a multi-factorial syndrome caused by interactions between genetic, physiological, environmental, and managemental factors. It was estimated that ascites accounts for losses of about US$1 billion annually worldwide and for over 25% of broilers mortality. Although traditional and molecular genetic methods in the selection and in performance improvements, has greatly reduced ascites frequency, yet it has ...


Role Of P300 Zz Domain In Chromatin Association And Histone Acetylation, Yongming Xue Dec 2018

Role Of P300 Zz Domain In Chromatin Association And Histone Acetylation, Yongming Xue

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Transcription is strictly regulated by numerous factors including transcription coactivators. The p300 protein and its close paralogue CREB-binding protein (CREBBP, aka CBP) are well-known transcriptional coactivators that have intrinsic lysine acetyltransferase activity. The functions of p300/CBP largely rely on their capabilities to bind to chromatin and to acetylate the histone substrates. However, the molecular mechanisms underlying the regulation of these processes are not fully understood.

Through combination of various biochemical, biophysical and molecular approaches, we show that the ZZ-type zinc finger (ZZ) domain of p300 functions as a histone reader that specifically binds the N-terminal tail of histone H3 ...


The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland May 2018

The Regulation Of Dna Methylation In Mammalian Development And Cancer, Nicolas Veland

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

DNA methylation is an essential epigenetic modification in mammals, as it plays important regulatory roles in multiple biological processes, such as gene transcription, maintenance of chromosomal structure and genomic stability, genomic imprinting, retrotransposon silencing, and X-chromosome inactivation. Dysregulation of DNA methylation is associated with various human diseases. For example, cancer cells usually show global hypomethylation and regional hypermenthylation, which have been implicated in genomic instability and tumor suppressor silencing, respectively. Although great progress has been made in elucidating the biological functions of DNA methylation over the last several decades, how DNA methylation patterns and levels are regulated and dysregulated is ...


Investigation Of Alcohol-Induced Changes In Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics, Crystina Leah Kriss Apr 2018

Investigation Of Alcohol-Induced Changes In Hepatic Histone Modifications Using Mass Spectrometry Based Proteomics, Crystina Leah Kriss

Graduate Theses and Dissertations

Alcohol liver disease (ALD) is a major health concern throughout the world. Currently, in the United States, 17 million people suffer from alcoholism, of which 1.4 million people are receiving treatment [1, 2]. The link between ethanol metabolism, reactive oxygen species (ROS) and liver injury in ALD has been well characterized over the last couple decades [3-10]. Ethanol metabolism relies on the availability of the cofactor NAD+ for the oxidation of ethanol into acetate, consequently causing alterations in redox potential. Redox dysfunction within the mitochondria can affect multiple pathways important in maintaining cellular homeostasis. Chapter 1 provides an introduction ...


Investigating The Interplay Of Physiological And Molecular Mechanisms Underpinning Programmable Aspects Of Heat Stress In Pigs, Jacob Seibert Jan 2018

Investigating The Interplay Of Physiological And Molecular Mechanisms Underpinning Programmable Aspects Of Heat Stress In Pigs, Jacob Seibert

Graduate Theses and Dissertations

Heat stress (HS) undermines production efficiency in all animal agriculture, culminating in major economic losses annually. The effects of HS in pigs is realized through depressed growth, altered body composition, and impaired reproductive performance. Pigs, unlike other mammals, do not possess functional sweat glands, making them rely on other mechanisms to thermoregulate during a heat challenge. Continual investigation of hyperthermia in pigs is crucial for developing new strategies and/or technologies that mitigate the effects of HS imposed on the pork industry. The studies conducted in this dissertation investigate the complex interplay of whole-animal physiology as well as cellular and ...


Exploring The Role Of Tet1 In Genomic Imprinting, Jennifer Myers Sanmiguel Jan 2018

Exploring The Role Of Tet1 In Genomic Imprinting, Jennifer Myers Sanmiguel

Publicly Accessible Penn Dissertations

DNA methylation is an essential epigenetic mark crucial for normal mammalian development. This modification controls the expression of a unique class of genes, designated as imprinted, which are expressed monoallelically and in a parent-of-origin-specific manner. Proper parental allele-specific DNA methylation at imprinting control regions (ICRs) is necessary for appropriate imprinting. Processes that deregulate DNA methylation of imprinted loci cause disease in humans. DNA methylation patterns dramatically change during mammalian development: first, the majority of the genome, with the exception of ICRs, is demethylated after fertilization, and subsequently undergoes genome-wide de novo DNA methylation. Secondly, after primordial germ cells are specified ...


Characterizing The Requirement Of The Cmi/Trr Compass-Like Complex During Drosophila Development, Timothy Nickels Jan 2018

Characterizing The Requirement Of The Cmi/Trr Compass-Like Complex During Drosophila Development, Timothy Nickels

Master's Theses

The MLR family of COMPASS-like complexes are histone methyltransferase complexes that are associated with the activation of gene enhancers. In D. melanogaster, Cara mitad (Cmi, also known as Lpt) and Trithorax related (Trr) are central subunits of a complex orthologous to mammalian Lysine methyltransferase 2 C and D (KMT2C and KMT2D, also known as MLL3 and MLL2/4) that catalyze H3K4 monomethylation. Previous studies have demonstrated that mutations in these genes are associated with cancer and developmental disorders, but the mechanisms by which these alterations contribute to disease states are unknown. The Cmi-containing COMPASS-like complex and orthologous vertebrate complexes have ...


The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers Aug 2017

The Dlk1-Meg3 Locus In Malignant Cells Of Proposed Primordial Germ Cell Origins., Zachariah Payne Sellers

Electronic Theses and Dissertations

Primordial germ cells (PGCs) are hypothesized to deposit hematopoietic stem cells (HSCs) along their migration route through the embryo during the early stages of embryogenesis. PGCs also undergo global chromatin remodeling, including the erasure and reestablishment of genomic imprints, during this migration. While PGCs do not spontaneously form teratomas, their malignant development into germ cell tumors (GCTs) in vivo is often accompanied by the retention of hypomethylation at the IGF2-H19 imprinting control differentially methylated region (DMR). Previous studies in bimaternal embryos determined that proper genomic imprinting at two paternally imprinted loci was necessary for their growth and development: Igf2-H19 and ...


Cytosolic Acetyl-Coa Promotes Histone H3 Lysine 27 Acetylation In Arabidopsis, Chen Chen Feb 2017

Cytosolic Acetyl-Coa Promotes Histone H3 Lysine 27 Acetylation In Arabidopsis, Chen Chen

Electronic Thesis and Dissertation Repository

Acetyl-coenzyme A (acetyl-CoA) serves as a central metabolite in energy metabolism and biosynthesis. High level of acetyl-CoA can fuel the tricarboxylic acid (TCA) cycle to generate energy and store excess energy in fatty acids. Meanwhile, it also provides acetyl groups for protein acetylation, which normally occurs at the lysine or arginine residues. Acetylation regulates protein functions largely due to the change of total charges. Acetylation of histones, for example, can lead to loss of the interaction between histone and DNA, thus relaxing chromatin structure and potentially promoting gene expression. However, whether and how acetyl-CoA regulates plant chromatin remains unexplored. Here ...


Histone Variant Macroh2a In The Gut And Beyond: A Study Of Intestinal Fortitude, Ryan James Cedeno Jan 2017

Histone Variant Macroh2a In The Gut And Beyond: A Study Of Intestinal Fortitude, Ryan James Cedeno

Publicly Accessible Penn Dissertations

Epigenetic factors guide chromatin remodeling during cell state transitions and confer resistance to genotoxic stressors that could induce deleterious transformations. A particularly peculiar component of the epigenome with emerging roles in fine-tuning cell identity and upholding genomic stability is the structural histone variant macroH2A. Relatively little is currently known about macroH2A’s influence on overall cell developmental potency and less still is known about macroH2A’s contributions to adult stem cell identity and function in vivo. In this work, we use induced pluripotent stem cell (iPSC) reprogramming and the murine intestinal stem cell (ISC) system to model macroH2A’s overall ...


Epigenetic Characterization Of Human Retina Cells, Nicholas R. Dunham May 2016

Epigenetic Characterization Of Human Retina Cells, Nicholas R. Dunham

Senior Honors Projects, 2010-2019

DNA methylation is an epigenetic modifier that modulates gene expression in plant and vertebrate genomes. The aim of this study was to characterize the role of DNA methylation in the human retina, particularly within rod and cone photoreceptor retinal neurons. Previous studies investigating DNA methylation in murine retinal cells and retina-derived human retinoblastoma immortalized cell culture lines demonstrate an inverse relationship between DNA methylation and transcriptional activity. Here, we used gene-specific bisulfite pyrosequencing analysis to measure DNA methylation in the genomes of human ocular cells in an effort to characterize the role of this important epigenetic modifier. These results can ...


Preeclampsia: The Roles Of Acute Inflammation And Intrauterine Stress, Nicholas Parchim May 2016

Preeclampsia: The Roles Of Acute Inflammation And Intrauterine Stress, Nicholas Parchim

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Preeclampsia (PE) is a severe, acute disease of pregnancy affecting approximately 8% of pregnant women after week 20 of gestation. PE is characterized by hypertension and renal damage reflected by proteinuria and has significant morbidity to both mother and fetus. Maternal symptoms range from headaches, nausea, edema, to visual changes, but once maternal symptoms present, damage to the fetus has begun. Mothers who progress untreated through the disease can also experience a condition called eclampsia characterized by seizure, coma, and, ultimately, death. PE-affected newborns experience features similar to prematurity—abnormal lung and renal development, intrauterine growth retardation (IUGR), and, possibly ...


Epigenetic Regulation Of The Dlk1-Meg3 Imprinted Locus In Human Islets, Vasumathi Kameswaran Jan 2016

Epigenetic Regulation Of The Dlk1-Meg3 Imprinted Locus In Human Islets, Vasumathi Kameswaran

Publicly Accessible Penn Dissertations

Type 2 diabetes mellitus (T2DM) is a complex metabolic disease characterized by inadequate insulin secretion by the pancreatic β-cell in response to increased blood glucose levels. Despite compelling evidence that T2DM has a high rate of familial aggregation, known genetic risk variants account for less than 10% of the observed heritability. Consequently, post-transcriptional regulators of gene expression, including microRNAs and other noncoding RNAs, have been implicated in the etiology of T2DM, in part due to their ability to simultaneously regulate the expression of hundreds of targets.

To determine if microRNAs are involved in the pathogenesis of human T2DM, I sequenced ...


Linking Acetyl-Coa Metabolism And Histone Acetylation To Dynamic Gene Regulation In Yeast And Mouse Hippocampus, Philipp Mews Jan 2016

Linking Acetyl-Coa Metabolism And Histone Acetylation To Dynamic Gene Regulation In Yeast And Mouse Hippocampus, Philipp Mews

Publicly Accessible Penn Dissertations

A compelling body of evidence suggests an intimate relationship between metabolic state and chromatin regulation. This link is manifested in key metabolites that participate in biochemical pathways as intermediates, and function as cofactors to regulate chromatin modifying enzymes. Of particular interest is the metabolite acetyl-CoA, given its central role as an intermediate of cellular energy metabolism and key determinant of all histone acetylation. How nuclear acetyl-CoA levels are regulated to, in turn, control histone acetylation is under intense investigation, and holds promise for increased understanding of the molecular mechanisms adapting gene expression to internal and external stimuli. We studied the ...


Deciphering The Tetrad Of Epigenetic Cytosine Modifications, Monica Yun Liu Jan 2016

Deciphering The Tetrad Of Epigenetic Cytosine Modifications, Monica Yun Liu

Publicly Accessible Penn Dissertations

A tetrad of epigenetic cytosine modifications imbues the DNA code with complex, dynamic meaning. DNA methyltransferase enzymes deposit methyl marks on the 5-carbon of cytosine, forming 5-methylcytosine (mC), which generally mediates long-term, locus-specific transcriptional repression during development and reprogramming. Ten-eleven translocation (TET) family enzymes oxidize the methyl group in three steps, forming predominantly 5-hydroxymethylcytosine (hmC) but also low levels of 5-formylcytosine (fC) and 5-carboxylcytosine (caC). These additional bases likely provide pathways for erasing methylation, but they may also harbor epigenetic functions in their own right. Questions regarding how each base forms and functions drive at the fundamental biology of the ...


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 ...


Interplay Between P53 And Epigenetic Pathways In Cancer, Jiajun Zhu Jan 2016

Interplay Between P53 And Epigenetic Pathways In Cancer, Jiajun Zhu

Publicly Accessible Penn Dissertations

The human TP53 gene encodes the most potent tumor suppressor protein p53. More than half of all human cancers contain mutations in the TP53 gene, while the majority of the remaining cases involve other mechanisms to inactivate wild-type p53 function. In the first part of my dissertation research, I have explored the mechanism of suppressed wild-type p53 activity in teratocarcinoma. In the teratocarcinoma cell line NTera2, we show that wild-type p53 is mono-methylated at Lysine 370 and Lysine 382. These post-translational modifications contribute to the compromised tumor suppressive activity of p53 despite a high level of wild-type protein in NTera2 ...


An Analysis Of The Interaction Between Sin3 And Methionine Metabolism In Drosophila, Mengying Liu Jan 2016

An Analysis Of The Interaction Between Sin3 And Methionine Metabolism In Drosophila, Mengying Liu

Wayne State University Dissertations

Chromatin modification and cellular metabolism are tightly connected. The mechanism for this cross-talk, however, remains incompletely understood. SIN3 controls histone acetylation through association with the histone deacetylase RPD3. In this study, my major goal is to explore the mechanism of how SIN3 regulates cellular metabolism.

Methionine metabolism generates the major methyl donor S-adenosylmethionine (SAM) for histone methylation. In collaboration with others, I report that reduced levels of some enzymes involved in methionine metabolism and histone demethylases lead to lethality, as well as wing development and cell proliferation defects in Drosophila melanogaster. Additionally, disruption of methionine metabolism can directly affect histone ...


The Role Of Thymine Dna Glycosylase (Tdg) And Dna Demethylation In Tgf Beta Signaling, Matthew E.R. Maitland Dec 2015

The Role Of Thymine Dna Glycosylase (Tdg) And Dna Demethylation In Tgf Beta Signaling, Matthew E.R. Maitland

Electronic Thesis and Dissertation Repository

Prompted by findings that TGFβ stimulates thymine DNA glycosylase (TDG) dependent rapid DNA demethylation and activation of the CDKN2B gene, I investigated the global role of TDG and DNA demethylation in TGFβ signaling in HaCaT cells. Using dot blot analysis, I show that TGFβ treatment increases the global levels of 5-formylcytosine, an intermediate metabolite of active DNA demethylation. Characterization of genomic regions that undergo DNA demethylation and recruitment of TDG indicate that they are both frequent events, but only overlap at 11 genomic locations. I identified 440 TGFβ upregulated genes, 40 of which were bound by TDG and 169 that ...


Dnmt1 In Intestinal Development And Cancer, Ellen Nichole Elliott Jan 2015

Dnmt1 In Intestinal Development And Cancer, Ellen Nichole Elliott

Publicly Accessible Penn Dissertations

Patterns of DNA methylation are established and maintained by DNA methyltransferases (Dnmts), which have traditionally been subdivided into the ‘de novo’ methyltransferases, Dnmt3a and Dnmt3b, and the ‘maintenance’ methyltransferase, Dnmt1. Dnmt1 maintains DNA methylation patterns and genomic stability in several in vitro cell systems, but its function in tissue-specific development, homeostasis, and disease in vivo is only beginning to be investigated.

Recently, the Kaestner lab demonstrated that loss of Dnmt1 in the adult intestinal epithelium causes a two-fold expansion of the proliferative crypt zone, indicating that Dnmt1 and DNA methylation regulate proliferative processes in the intestine. I hypothesized that loss ...


Epigenetic Interplay Between Histone H3k9me2 And Jil-1 Mediated Histone H3s10ph, Chao Wang Jan 2014

Epigenetic Interplay Between Histone H3k9me2 And Jil-1 Mediated Histone H3s10ph, Chao Wang

Graduate Theses and Dissertations

In Drosophila, JIL-1 Kinase specifically localizes to euchromatic interband regions of polytene chromosomes and is responsible for histone H3S10 phosphorylation at interphase. Previous genetic interaction assays have demonstrated that the JIL-1 protein can counterbalance the effect of the major heterochromatin components Su(var)3-7 on position-effect variegation (PEV). In this study, we show that the haplo-enhancer effect of JIL-1 has the ability to counterbalance the haplo-suppressor effect of two other major heterochromatin components, Su(var)3-9 and Su(var)2-5, on position-effect variegation, providing evidence that a finely tuned balance between the levels of JIL-1 and the major heterochromatin components ...


The Regulation Of Gene Expression During Memory Consolidation In The Hippocampus, Shane Gary Poplawski Jan 2014

The Regulation Of Gene Expression During Memory Consolidation In The Hippocampus, Shane Gary Poplawski

Publicly Accessible Penn Dissertations

Memory consolidation is the process through which short-term memories are stabilized for long-term retention. New gene expression is required for this process to occur successfully. Although gene expression is a necessary component for memory consolidation, the targets and regulation of this gene expression are not well understood. The advent of next-generation sequencing technologies has provided a tremendous resource to probe important questions genome-wide in ways that were previously impossible. In this dissertation, I use next-generation sequencing to investigate the transcriptional targets of learning in the hippocampus. Chapter 1 reviews the previous research on the regulation of gene expression during memory ...


Proximate And Evolutionary Insights Into The Epigenetics Of Posttraumatic Stress Disorder, Levent Sipahi Jan 2014

Proximate And Evolutionary Insights Into The Epigenetics Of Posttraumatic Stress Disorder, Levent Sipahi

Wayne State University Dissertations

Posttraumatic stress disorder (PTSD) is an important medical and social condition. Although the vast majority of individuals are exposed to traumatic events within their lifetime, a minority subsequently develop diagnosable PTSD. What underlies differential risk and resiliency in the face of trauma is an ongoing research and clinical question with implications for prevention and treatment. Recent work has revealed a putative role of epigenetic variation and modification - most notably DNA methylation - in the etiology of PTSD. That DNA methylation is stable, yet modifiable in response to lived experiences, makes it a strong candidate to mechanistically explain the ontogeny of PTSD ...


Structural And Functional Characterization Of The Mbd2-Nurd Co-Repressor Complex, Megha Desai Jan 2014

Structural And Functional Characterization Of The Mbd2-Nurd Co-Repressor Complex, Megha Desai

Theses and Dissertations

The MBD2-NuRD co-repressor complex is an epigenetic regulator of the developmental silencing of embryonic and fetal β-type globin genes in adult erythroid cells as well as aberrant methylation-dependent silencing of tumor suppressor genes in neoplastic diseases. Biochemical characterization of the MBD2-NuRD complex in chicken erythroid cells identified RbAp46/48, HDAC1/2, MTA1/2/3, p66α/β, Mi2α/β and MBD2 to comprise this multi-protein complex.

In the work presented in Chapter 2, we have pursued biophysical and molecular studies to describe a previously uncharacterized domain of human MBD2 (MBD2IDR). Biophysical analyses show that MBD2IDR is an intrinsically disordered ...


Molecular Mechanisms Underlying The Early Life Programming Of The Liver, Gurjeev Sohi Jul 2013

Molecular Mechanisms Underlying The Early Life Programming Of The Liver, Gurjeev Sohi

Electronic Thesis and Dissertation Repository

Clinical studies have demonstrated that intrauterine growth restriction (IUGR) offspring, faced with a nutritional mismatch postpartum, have an increased risk of developing the metabolic syndrome. The maternal protein restriction (MPR) rat model has been extensively studied to investigate the adverse effects of a nutritional mismatch in postnatal life of IUGR offspring. Previous studies have demonstrated that MPR leads to impaired function of the liver, an important metabolic organ. However the underlying mechanisms which predispose these offspring to the metabolic syndrome remain elusive. In the following studies, low protein diet during pregnancy and lactation led to IUGR offspring with decreased liver ...


Genome-Wide Profiling Unveils Criticial Functions Of P53 In Human Embryonic Stem Cells, Kadir C. Akdemir May 2013

Genome-Wide Profiling Unveils Criticial Functions Of P53 In Human Embryonic Stem Cells, Kadir C. Akdemir

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Embryonic stem cells (ESCs) possess two unique characteristics: infinite self-renewal and the potential to differentiate into almost every cell type (pluripotency). Recently, global expression analyses of metastatic breast and lung cancers revealed an ESC-like expression program or signature, specifically for cancers that are mutant for p53 function. Surprisingly, although p53 is widely recognized as the guardian of the genome, due to its roles in cell cycle checkpoints, programmed cell death or senescence, relatively little is known about p53 functions in normal cells, especially in ESCs. My hypothesis is that p53 has specific transcription regulatory functions in human ESCs (hESCs) that ...


Cellular Adaptation Of Macrophages To Anthrax Lethal Toxin-Induced Pyroptosis Via Epigenetic Mechanisms, Chae Young Han Apr 2013

Cellular Adaptation Of Macrophages To Anthrax Lethal Toxin-Induced Pyroptosis Via Epigenetic Mechanisms, Chae Young Han

Electronic Thesis and Dissertation Repository

Cellular adaptation to microbial stresses has been demonstrated in several cell types. Macrophages (MФ) are sentinel immune cells fending off invading microbes. Anthrax lethal toxin (LeTx) is a key virulence factor released by Bacillus anthracis that causes rapid cell death, pyroptosis. A small number of RAW246.7 macrophages (~4%) exposed to a non-lethal dose of LeTx become resistant to LeTx-induced pyroptosis for ~ 4 weeks, termed “toxin-induced resistance (TIR)”. Here, I showed that high levels of DNA methyl transferase1 (DNMT1) expression were maintained although global genomic methylation levels were not high in TIR. TIR cells treated with the DNMT inhibitor 5-azacitidine ...