Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 34 for “"DNMT3A"”.
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DNMT3a Epigenetic Program Regulates the HIF-2alpha Oxygen Sensing Machinery
… We show that DNA methyltransferase 3a (DNMT3a) methylates and silences the HIF-2alpha gene (EPAS1) in normal cells. Epigenetic silencing of EPAS1 prevents activation of the HIF-2alpha gene program associated with hypoxic cell growth, thereby limiting the proliferative capacity of cells …
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Regulation of De Novo and Maintenance Dna Methylation By Dnmt3A and Dnmt3B
… two classes of DNA methyltransferases (DNMTs): DNMT3A and DNMT3B function primarily as <em>de novo</em> methyltransferases that establish DNA methylation patterns, whereas DNMT1 is the major enzyme responsible for maintaining DNA methylation patterns by converting hemi-methylated CpGs to fully …
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The role of the de novo DNA methyltransferase Dnmt3a in the nervous system
… disruption of the de novo DNA methyltransferase Dnmt3a in mice were used to elucidate the role of the enzyme in the nervous system. Inactivating Dnmt3a in the nervous system resulted in a drastically shortened lifespan and in behavioral abnormalities that suggested a motor defect. Dnmt3a mutants …
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The role of the PWWP domain in the DNA methyltransferase 3A targeting to the genome
… of DNMTs. In particular, the PWWP domains of DNMT3A and DNMT3B are posited to interact with histone 3 lysine 36 trimethylation (H3K36me3). In this study, I characterise a mouse model carrying a D329A point mutation in the DNMT3A PWWP domain, predicted to ablate the DNMT3A-PWWP and H3K36me3 …
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Molecular Characterization of Mammalian De Novo DNA Methyltransferase Chromatin Recruitment
… of de novo DNA methyltransferases 3A (DNMT3A) and 3B (DNMT3B) is facilitated in part by chromatin "reader" domains to establish DNA methylation patterns genome-wide. Recent work has highlighted a role for the PWWP reader domain in directing recruitment of DNMT3B to actively transcribed …
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The Effects of Methyltransferase Genes on Human Haematopoietic Stem Cell Function
… focused on 2 methyltransferase genes, PRMT5 and DNMT3A, which are both epigenetic modulators of HSC function. Pharmacological inhibition of PRMT5 in healthy human cord blood (hCB) haematopoietic stem and progenitor cells (HSPCs) leads to reduced HSPC proliferation and a relative differentiation …
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The Role of DNA Methylation in Addiction and Depression
… remain poorlyunderstood. I found that Dnmt3a expression is persistently regulated in nucleus accumbens (NAc),a key brain reward region, by chronic cocaine or chronic social defeat stress. Moreover, NAc specific manipulations that block DNA methylation potentiate cocaine reward and exert …
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The role of the Dnmt3aR882H mutation in the evolution of clonal haematopoiesis.
DNMT3A mutations are very frequent events in clonal haematopoiesis of indeter- minate potential (CHIP), and considered one of the earliest genetic events during the development of haematopoietic malignancies. Individuals with CHIP, in spite of having a normal full blood count are at increased risk …
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An investigation of the epigenetic and transcriptional changes which follow Epstein-Barr virus infection of germinal centre B cells
… the up-regulation of the DNA methyltransferases, DNMT3A, and the down-regulation of DNMT1 and DNMT3B, a pattern of expression which is re-capitulated in HL cell lines. I have also shown that the major EBV oncogene, LMP1, is responsible for the down-regulation in GC B cells of DNMT1, and that …
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Twist1 and Etv5 are part of a transcription factor network defining T helper cell identity
… that attenuates the gene-repressing activity of Dnmt3a. In the absence of STAT4, genetic loss of Dnmt3a results in de-repression of a subset of Th1 genes, and a partial increase in expression that is sufficient to observe a modest recovery of STAT4-dependent inflammatory disease. STAT4 also …
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Clonal haematopoiesis of indeterminate potential and the role of inflammation in its association with atherosclerosis
… are increased by Tet2 loss, and reduced by Dnmt3a mutation, despite both perturbations upregulating transcript for IL-1β. Conversely, Jak2 mutations have no effect on macrophage cytokine production or release. Therefore, immunomodulatory therapies under investigation for the cardiovascular …
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DNA methylation: the "stable" epigenetic mark
… is established de novo by DNA methyltransferases DNMT3A/3B and then faithfully maintained by DNMT1. Hence, intermediate methylation levels likely represent stochastic de novo establishment (DNMT3A/3B) and clonal maintenance (DNMT1) within the cell population. To test this, I subcloned single cells …
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The Regulation of Dna Methylation In Mammalian Development and Cancer
… regulator of de novo methylation, facilitates Dnmt3a-mediated methylation by stabilizing Dnmt3a2, the major Dnmt3a isoform in mESCs, thus uncovering a new role for Dnmt3L and providing a plausible explanation for the functional specificity of Dnmt3L. In a separate project, I demonstrate that …
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The natural history of clonal haematopoiesis
… different growth rates, ranging from 5% (DNMT3A, TP53) to over 50%/yr (SRSF2-P95H). Growth rates of clones with the same mutation differed by +/-5%/yr, proportionately impacting “slow” drivers more substantially. Combining these time-series data with phylogenetic analysis of 1,731 whole …
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The molecular mechanisms of pseudogene-mediated PTEN expression.
… of proteins including DNA-methyltransferase 3a (DNMT3a) and Enhancer of zeste homologue 2 (EZH2) have been found to repress the PTEN gene by interacting at the PTEN promoter to cause a complex set of epigenetic changes. Here we show that an additional, previously uncharacterised transcript exists …
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Epigenetic and Ubiquitin-Proteasome Mechanisms of Obesity Development
… Next, we used the CRISPR-dCas9-TET1 and dCas9-DNMT3a systems to test the role of Pomc DNA methylation in the hypothalamus in abnormal weight gain following acute exposure to a high fat diet in male rats. We found that exposure to a high fat diet increases Pomc DNA methylation and reduces gene …
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Application of High-Performance Liquid-Chromatography Mass-Spectrometry Platform to Study Metabolism and Epigenetic Control of Metabolism
… uninhibited. There are two de novo DNMTs, DNMT3A, and DNMT3B. These DNMTs establish the pattern of methylation. We examined de novo DNMT-mediated control of cellular metabolism, identifying global changes in metabolism, as well as differential sensitivity towards glycolytic and …
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EXPLORING THE MUTATIONAL LANDSCAPE OF MITOCHONDRIAL GENOME IN HEMATOLOGIC MALIGNANCIES
… co-occurrence of mtDNA variants with DNMT3A mutations in AML suggested possible nuclear-mitochondrial interactions. Targeted mitochondrial sequencing in cell lines validated recurrent variants and confirmed accurate detection of heteroplasmy levels. Finally, analysis of T lymphocytes …
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