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 31 for “"epigenetic landscape"”.
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Establishment of the epigenetic landscape in mammalian embryonic stem cells
… development. Deciphering the details of such epigenetic phenomena has the potential to enrich both stem cell biology and therapeutics, as well as offer insight into various pathologies. While the enzymatic machinery responsible for these transitions is well known, it is their localization to …
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Rejuvenation of The Epigenetic Landscape of The Aged Brain Through Manipulation of Circulating Factors
… we found that the aged brain becomes epigenetically dysregulated, with an increase in Ezh2 function and simultaneous loss of the opposing function of Jmjd3, thereby leading to a respective increase in H3K27me3 and decrease in H3K27me1 in the brain with age. Furthermore, when we …
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Global alterations of the epigenetic landscape define endometrial receptivity and provide a hallmark for endometriosis
… roles in reproduction. Perhaps the most dramatic epigenetic change is observed in endometrial epithelial cells that acquire high levels of 5hmC during the establishment of the receptive state. This increase of 5hmC correlates with increased gene expression, in particular at genes that are crucial …
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A CELL CYCLE CLOCK REGULATES THE EPIGENETIC LANDSCAPE OF AML CELLS AND DETERMINES SENSITIVITY TO LSD1 INHIBITION
… of AML biology and treatment, focusing on the epigenetic enzyme LSD1, which is regularly found overexpressed in AML, as a therapeutic target. We revealed a crucial role for the cell cycle regulator p21 in determining sensitivity to LSD1 inhibition. Our findings further demonstrate that …
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Unravelling the epigenetic landscape of pancreatic cancer: The role of cancer-associated fibroblasts in transcription factor regulation
… by strong driver mutations, extensive epigenetic reprogramming, and a dense tumour microenvironment (TME). A defining feature of the PDAC TME is its fibrotic stroma, which is largely composed of cancer-associated fibroblasts (CAFs). Distinct populations of CAFs, including inflammatory …
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Characterization of Chronic Glucocorticoid Exposure on Natural Killer Cell Function: A Model for Stress Induced Alterations on the Epigenetic Landscape
… function through the modification of the epigenetic status of NK effector genes through HDAC redistribution and subsequent epigenetic changes in a promoter specific manner.</p><p>These observations were used to investigate the alterations in immune function during periods of psychological …
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Regulation of Chromatin Multi-Scale Organization and Function by Linker Histone H1
… disruption of higher-order chromatin structure, epigenetic landscape, and, to varying degrees, gene regulation. Here, we show that acute H1 depletion results in decompaction of the chromatin fiber, accompanied by transcriptional derepression and increased chromatin accessibility. In contrast to …
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Context-dependent activity of a pioneer transcription factor, ASCL1, in early development
… about the sensitivity of pioneer TFs to the epigenetic landscape. Moreover, the epigenome is remodelled during the exit from pluripotency, and it is not well understood how these changes in turn influence the activity of lineage-specifying pioneer TFs. This project sets out to address these …
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Stochastic Activation of Enhancers in the Innate Immune Response by the Histone Demethylase JMJD2D
… of dozens of chromatin modifiers to establish an epigenetic landscape permissive of gene transcription. Among the most dynamic histone modifications are the acetylation and methylation at histone 3 lysine 9, but the precise roles of their modifiers in conserved transcriptional programs remain …
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STEPWISE DIFFERENTIATION OF IL21-PRODUCING FOLLICULAR HELPER T CELLS REVEALS DISTINCT DEVELOPMENTAL AND FUNCTIONAL STATES
… marked by loss of IL-21. The transcriptional and epigenetic landscape is formed in the earlyTfh21 stage and is maintained throughout the exTfh21 state, suggesting terminal differentiation. We also clarify that the transcription factor Foxp1 intrinsically regulates the transition between these …
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Regulating Inflammation Through Exercise-Mediated Trained Immunity or Genetic Manipulation of the Interferon Locus
… in immune cells due to persistent metabolic and epigenetic changes. Data from this study suggest that chronic moderate exercise can influence the inflammatory responses of macrophages by reprogramming their metabolic and epigenetic landscape. Second, we evaluated the role of specific type I …
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On the epigenetic ageing clock in humans
Epigenetic clocks are mathematical models that predict the biological age of an organism using DNA methylation data, and which have emerged in the last few years as the most accurate biomarkers of the ageing process. However, little is known about the molecular mechanisms that control the rate of …
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Modelling metabolic landscapes in human naive and primed embryonic stem cells
… cell states also show major differences in their epigenetic landscape including in DNA methylation, repressive histone modifications, and spatial organisation of chromatin. I am interested in studying this metabolic regulation and its potential interface with epigenetic modifiers. In order to …
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Molecular Mechanisms Behind Sars-Cov-2 Induced Host Genome Restructuring
… alterations in 3D genome organization and epigenetic landscape following SARS-CoV-2 infection that are distinct from and more severe than changes caused by other viral infections or immune stimulants. While these changes at the chromatin level are important for understanding the immune …
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The Polycomb Complex 2 contributes to developmental delay when histone methylation is inappropriately inherited
… must undergo maternal reprogramming to reset the epigenetic landscape in the new zygote. During maternal reprogramming of histone methylation in <em>C. elegans</em>, H3K4me is removed by the H3K4 demethylase, SPR-5, and H3K9me is subsequently added by the histone methyltransferase, MET-2. …
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Transcriptional Regulation of Neonatal Heart Regeneration and Direct Cardiac Reprogramming
… exposes underlying dynamics of open chromatin landscapes and regenerative gene regulatory networks of diverse cardiac cell types, and reveals previously unknown extracellular mediators of cardiomyocyte proliferation, angiogenesis, and fibroblast activation. Furthermore, using single-nucleus RNA …
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CHARACTERISING THE REPROGRAMMING DYNAMICS BETWEEN HUMAN PLURIPOTENT STATES
… transcriptional changes and remodelling of the epigenetic landscape that occurs during the reprogramming process. To address this knowledge gap, I sought to develop an isolation strategy capable of identifying nascent naïve hPSCs early during reprogramming. Comprehensive profiling of …
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Activin/Nodal Signalling Controls the Epigenome and Epitranscriptome of Human Pluripotent Stem Cells
… I show that SMAD2/3 modulates the chromatin epigenetic landscape of hPSCs by cooperating with the pluripotency factor NANOG to recruit the DPY30-COMPASS complex and promote histone 3 lysine 4 trimethylation (H3K4me3). This regulation promotes expression of pluripotency genes, while poising …
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The role of Arid1a and Tet1 in ductal cell-driven liver regeneration
… Using knock down experiments, we identified the epigenetic modifiers Arid1a and Tet1 as important candidates for ductal progenitor maintenance and establishment, respectively, in vitro. Further in vitro analysis of several genetic models of Arid1a showed that reduction but not ablation of Arid1a …
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