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Molecular Biology

The Texas Medical Center Library

Epigenetics

Articles 1 - 7 of 7

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

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

UT GSBS 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

UT GSBS 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 ...


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

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

UT GSBS 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 ...


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

UT GSBS 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 ...


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 ...


Definition Of The Landscape Of Chromatin Structure At The Frataxin Gene In Friedreich’S Ataxia, Eunah Kim Dec 2011

Definition Of The Landscape Of Chromatin Structure At The Frataxin Gene In Friedreich’S Ataxia, Eunah Kim

UT GSBS Dissertations and Theses (Open Access)

Friedreich’s ataxia (FRDA) is caused by the transcriptional silencing of the frataxin (FXN) gene. FRDA patients have expansion of GAA repeats in intron 1 of the FXN gene in both alleles. A number of studies demonstrated that specific histone deacetylase inhibitors (HDACi) affect either histone modifications at the FXN gene or FXN expression in FRDA cells, indicating that the hyperexpanded GAA repeat may facilitate heterochromatin formation. However, the correlation between chromatin structure and transcription at the FXN gene is currently limited due to a lack of more detailed analysis. Therefore, I analyzed the effects of the hyperexpanded GAA repeats ...


Xenoestrogen-Specific Mechanisms Of Developmental Reprogramming Correlate With Gene Expression And Tumor Development, Kristen L. Greathouse May 2010

Xenoestrogen-Specific Mechanisms Of Developmental Reprogramming Correlate With Gene Expression And Tumor Development, Kristen L. Greathouse

UT GSBS Dissertations and Theses (Open Access)

Environmental exposures during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life in a process known as developmental reprogramming. We have shown that neonatal exposure to the xenoestrogen diethylstilbestrol (DES) can developmentally reprogram the reproductive tract in genetically susceptible Eker rats giving rise to complete penetrance of uterine leiomyoma. Based on this, we hypothesized that xenoestrogens, including genistein (GEN) and bisphenol A (BPA), reprogram estrogen-responsive gene expression in the myometrium and promote the development of uterine leiomyoma. We proposed the mechanism that is responsible for the developmental reprogramming of gene expression was through ...