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Articles 1 - 13 of 13
Full-Text Articles in Entire DC Network
Definition Of The Landscape Of Chromatin Structure At The Frataxin Gene In Friedreich’S Ataxia, Eunah Kim
Definition Of The Landscape Of Chromatin Structure At The Frataxin Gene In Friedreich’S Ataxia, Eunah Kim
Dissertations & 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 …
Role Of Hdacs And Sam In Interferon-Alpha Signaling And Epigenetic Regulation Of Anti-Hcv Gene Expression., Stephanie A. Mathews
Role Of Hdacs And Sam In Interferon-Alpha Signaling And Epigenetic Regulation Of Anti-Hcv Gene Expression., Stephanie A. Mathews
Electronic Theses and Dissertations
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease in the United States and is a huge burden on the US healthcare system. The FDA-approved traditional standard of care for HCV is pegylated interferon-alpha (lFNa) combined with ribavirin, which is effective in about 50% of patients. The molecular mechanisms involved in resistance to IFNa therapy remain unclear. Recent data strongly suggest that histone deacetylases (HDACs) and methylation play critical roles in the regulation of IFNa anti-HCV signaling and gene expression. The present work was carried out to elucidate the roles of HDACs and S-adenosylmethionine (SAM) metabolism …
Epigenetic Regulations In Cell Wall Degradation And Regeneration In Oryza Sativa, Feng Tan
Epigenetic Regulations In Cell Wall Degradation And Regeneration In Oryza Sativa, Feng Tan
Theses and Dissertations
It is well known that chromatin components are key players in establishing and maintaining spatial and temporal gene expression in plants, however, little is known about the epigenetic regulation on cell wall degradation and regeneration. This study aimed to 1) investigate the global proteome and phosphoproteome of rice chromatin, and 2) characterize changes in chromatin components and chromatin structure associated with cell wall degradation and regeneration, and 3) characterize the differentially regulated proteins and eventually explore the mechanism. In this dissertation, we examine proteins copurified with chromatin using both 2-DE gel and shotgun approaches from rice (Oryza sativa) suspension cells. …
Mechanism Of Transcriptional Suppression Of A Phytochrome A Epiallele In Arabidopsis Thaliana, Gulab D. Rangani
Mechanism Of Transcriptional Suppression Of A Phytochrome A Epiallele In Arabidopsis Thaliana, Gulab D. Rangani
Graduate Theses and Dissertations
Cytosine methylation in DNA is an integral part of epigenetically controlled regulatory networks in eukaryotes. Both plants and vertebrates display DNA methylation in the gene coding region; however, its role in gene expression is not well understood. Gene promoter, on the other hand, remains largely unmethylated. Acquisition of methylation in promoter results in transcriptional suppression of the gene. The goal of this research is to study the effect of coding region methylation in gene expression using a unique gene model, phyA'. phyA' is a transcriptionally suppressed epiallele of the Arabidopsis thaliana Phytochrome A gene, which contains methylation in CG sites …
Prediction Of Dna Methylation Based On Genomic Architecture And Applications Of Positional Weight Matrices, Juan Gallegos
Prediction Of Dna Methylation Based On Genomic Architecture And Applications Of Positional Weight Matrices, Juan Gallegos
Dissertations & Theses (Open Access)
Gene silencing due to epigenetic mechanisms shows evidence of significant contributions to cancer development. We hypothesis that the genetic architecture based on retrotransposon elements surrounding the transcription start site, plays an important role in the suppression and promotion of DNA methylation. In our investigation we found a high rate of SINE and LINEs retrotransposon elements near the transcription start site of unmethylated genes when compared to methylated genes. The presence of these elements were positively associated with promoter methylation, contrary to logical expectations, due to the malicious effects of retrotransposon elements which insert themselves randomly into the genome causing possible …
The Effects Of Superovulation And Embryo Culture On Genomic Imprinting In A Mouse Model System, Brenna A. M. Velker
The Effects Of Superovulation And Embryo Culture On Genomic Imprinting In A Mouse Model System, Brenna A. M. Velker
Electronic Thesis and Dissertation Repository
Genomic imprinting is a specialized transcriptional mechanism resulting in the unequal expression of alleles based on their parent-of-origin. Imprinted genes are critical for embryonic and fetal development and their dysregulation is linked to a group of human diseases called imprinting disorders, including Beckwith-Wiedemann Syndrome, Angelman Syndrome and Silver-Russell Syndrome. Two critical phases of genomic imprinting exist. The acquisition phase occurs in developing germ cells, asynchronously for different imprinted loci, while the maintenance phase takes place during preimplantation development, while the rest of the genome is undergoing demethylation. Increased frequencies of human imprinting disorders are observed in children following the use …
Expression Analysis Of The Imprinted Gene Transketolase-Like 1 In Mouse And Human, Amy F. Friss
Expression Analysis Of The Imprinted Gene Transketolase-Like 1 In Mouse And Human, Amy F. Friss
Master's Theses
Genomic imprinting is an epigenetic phenomenon resulting in differential gene expression based on parental origin. Recently, transketolase-like 1 (TKTL1) has been identified as an X-linked imprinted gene. TKTL1 functions in the nonoxidative branch of the pentose phosphate pathway (PPP), which maintains glutathione in a reduced state through the generation of NADPH. Previous studies on transaldolase, the other critical enzyme in the nonoxidative branch of the PPP, suggest that TKTL1 may affect the cell’s ability to reduce glutathione. This study provides evidence that TKTL1 overexpression inhibits glutathione reduction. Intriguingly, aberrant glutathione levels are associated with autism. Additionally, studies involving …
Resilience Through Attending To The Power Of The Mind, Jennifer Dawn Behm
Resilience Through Attending To The Power Of The Mind, Jennifer Dawn Behm
Educational Specialist, 2009-2019
Abstract The science of psychological genomics, otherwise known as epigenetics, demonstrates how thoughts and emotions affect our physiology and even our genes. Genetic expression is a determining factor in many physical diseases and mental conditions. There is recent evidence that suggests that effective resilience-focused counseling may enable genes to express themselves in salubrious ways, frequently averting disease. Early counseling interventions can eliminate a future need for more costly invasive medical procedures. People can be mentally and physically healed when they are ministered to in their totality. The science of epigenetics has profound ramifications for all in the healing professions including …
The Specific Role Of The Mll Cxxc Domain In Mll Fusion Protein Function, Laurie Ellen Risner
The Specific Role Of The Mll Cxxc Domain In Mll Fusion Protein Function, Laurie Ellen Risner
Dissertations
The MLL gene was first identified because it is involved in chromosome translocations which produce novel fusion proteins that cause leukemia. The CXXC domain of MLL is a cysteine rich DNA binding domain with specificity for binding unmethylated CpG-containing DNA. The CXXC domain is retained in oncogenic MLL fusions, and is absolutely required for the fusions to cause leukemia. This project explored the role of the CXXC domain by introducing structure-informed point mutations within the MLL CXXC domain that disrupt DNA binding, and by performing domain swap experiments in which different CXXC domains from other proteins, including DNMT1, CGBP and …
Novel Inhibitors Of Lysine Specific Demethylase 1 As Epigenetic Modulators, Michael Crowley
Novel Inhibitors Of Lysine Specific Demethylase 1 As Epigenetic Modulators, Michael Crowley
Wayne State University Theses
The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 over expression is thought to contribute to the development of cancer. We recently reported a series of (bis)guanidines and (bis)biguanides that are potent inhibitors of LSD1, and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a new series of isosteres that are also potent inhibitors of LSD1. These compounds induce increases in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target …
Novel Role Of Mecp2 In Developing Oligodendrocytes And Myelination, Daniel Moore
Novel Role Of Mecp2 In Developing Oligodendrocytes And Myelination, Daniel Moore
Theses and Dissertations
Methyl-CpG-binding protein 2 (MeCP2 is) is an epigenetic regulator that binds to methylated DNA. Initially identified as transcriptional repressor, MeCP2 also binds to different proteins functioning as gene activator. Importantly, MecCP2 gene mutations and changes in MeCP2 levels are associated to several forms of mental retardation and autism-related disorders; including Rett, a neurodevelopmental disorder affecting primarily girls. While brain MeCP2 was considered to be exclusively neuronal, this regulator is also present in glia. We found that oligodendrocytes, the myelinating cells of the central nervous system (CNS), express particularly high MeCP2 levels at a developmental stage that precedes their final maturation. …
Characterization Of Pluripotency Factors In Human Umbilical Cord Blood Derived Multi Lineage Progenitor Cells Treated With Small Molecules, Heather Lindsay Mulholland
Characterization Of Pluripotency Factors In Human Umbilical Cord Blood Derived Multi Lineage Progenitor Cells Treated With Small Molecules, Heather Lindsay Mulholland
Digitized Theses
Induced pluripotent stem (iPS) cells have unparalleled potential for disease modeling and use in regenerative medicine but are plagued with genetic instability and tumourgenicity. Small molecules including histone deactylase inhibitors and DNA methylation inhibitors, as well as use of more undifferentiated cell types as source material, have been used to increase the efficiency and safety of reprogramming by necessitating fewer exogenous pluripotency factors. Human multi-lineage progenitor cells (hMLPCs), derived from post-partum umbilical cord blood, and human dermal fibroblasts (hDFs) were examined for both RNA expression and protein localization of pluripotency factors OCT4, SOX2, KLF4 and Nanog before and after 7-day …
Reactivation Of Estrogen Receptor-Α (Erα) By Bioactive Dietary Compounds Through Epigenetic Mechanisms In Erα-Negative Breast Cancer Cells, Shweta Naran Patel
Reactivation Of Estrogen Receptor-Α (Erα) By Bioactive Dietary Compounds Through Epigenetic Mechanisms In Erα-Negative Breast Cancer Cells, Shweta Naran Patel
All ETDs from UAB
In breast cancer treatment, the presence of the estrogen receptor-alpha (ERα) plays an important role with hormonal-responsive drugs such as tamoxifen. ERα-negative breast cancers are more aggressive not only because of the increased uncontrollable growth but also because of the lack of target-directed treatments. Bioactive dietary components such as green tea polyphenols (GTPs) and sulforaphane (SFN, found in cruciferous vegetables) have been shown to have anti-cancer properties. In this study, we found that the dietary combination of a DNA methyltransferases (DNMTs) inhibitor, GTPs, and a histone deacetylase (HDAC) inhibitor, SFN, dose-dependently inhibited the proliferation of ERα-negative MDA-MB-231 human breast cancer …