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 22 for “"Epigenetic modifiers"”.
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Regulation of the Kcnq1ot1 Imprinting Domain in Mouse
Genomic imprinting is an epigenetic mechanism that controls gene expression based on parental-origin of an allele. The Kcnq1ot1 imprinting cluster consists of an imprinting control region (ICR), the Kcnq1ot1 ncRNA, and maternally expressed protein-coding genes. Truncation of the Kcnq1ot1 ncRNA or …
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Exploiting Lentiviral Integrations to Profile Chromatin
… to dissect the recruitment requirements of key epigenetic modifiers, including BRD4 and the HUSH complex. Finally, I utilise a high-throughput screening approach to identify chromatin-binding domains of unknown specificities and exploit ChILI-seq to reveal their binding preferences. This screen …
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Identifying Novel Interactions Between Human Ubiquitin-Specific Protease 7 (USP7) and Histone Methylating/Demethylating Proteins
… response, DNA damage response, DNA replication, epigenetics and cell division. USP7s role in epigenetics is emerging and studies have demonstrated that USP7 modulates several epigenetic modifiers. This thesis further explores USP7s role in epigenetics, investigating USP7s novel regulation of two …
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CHD Chromatin Remodelers Promote Epigenetic Control of Development in Arabidopsis thaliana
… family of chromatin remodelers play key roles as epigenetic modifiers and transcriptional regulators in both plants and animals. PKL is a CHD3 remodeler that represses expression of seed genes during germination in Arabidopsis. Unlike animal CHD3 remodelers, PKL does not function as a member of a …
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Mechanism of Atrial Fibrillation in Lamin A/C Cardiomyopathy
… rhythm control and contractility. Using CRISPR epigenetic modifiers, we interrogate the function of several AF-associated regulatory regions and their target genes. Specifically, reduced accessibility at an SCN10A intronic enhancer harboring the AF-associated SNP, rs6801957, which is known to …
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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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EPIGENETIC MODIFICATIONS REGULATING LIVER HOMEOSTASIS AND TUMORIGENESIS
… identified, including signaling molecules and epigenetic modifiers. Specifically, mutations that affect the activity of SWI/SNF chromatin remodeling complex have been commonly reported. Mutational studies clearly indicated a role for epigenetic modifications in HCC development. However, it is …
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TRANSCRIPTIONAL NETWORKS VARIATIONS DURING CELL CYCLE PROGRESSION IN HUMAN EMBRYONIC STEM CELLS
… extra cellular signalling pathways with the epigenetic state, chromatin structure and transcriptional networks during cell cycle progression and these mechanisms remain to be fully uncovered. Here, I have utilised the FUCCI reporter system combined with ATAC-Seq to analyse chromatin dynamics …
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Enhancement of death receptor-mediated apoptosis in multiple myeloma cells
… lines and ADC-1 plasma cell leukaemia cells. All epigenetic modifiers and NEI synergistically enhanced TRAIL responses in several lines and responses were potentiated in 3D culture. Interestingly, TRAILR cells were sensitive to BIX 01294 and LMB; however, TRAIL responses in cells that had been …
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Harnessing DNA nanoarchitecture to overcome immunoevasion in cancer
… genes (STING) pathway; and (2) deliver epigenetic modifiers to reprogram immunosuppressive cues in tumor cells. This solution exploits the modularity, programmability, and ease of control over DNA synthesis to generate architectures that exhibit improved delivery kinetics and favorable …
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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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SMAD2/3 - FOXH1 regulation during cell cycle progression upon differentiation
… binding to developmental genes and co-recruiting epigenetic modifiers. Despite the importance of these interplay, the molecular mechanisms orchestrating transcriptional networks during progression of the cell cycle upon differentiation remain to be fully uncovered. In this dissertation, I combined …
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Towards elucidating the function of the oocyte Subcortical Maternal Complex: A multi-omic analysis of an Nlrp5-null murine model
… proteins altered in *Nlrp5*-null oocytes include epigenetic modifiers DNMT3L and UHRF1, both of which are reduced in the mutant, the former by over 75%, and the latter by 40%. Immunofluorescence analysis of *Nlrp5*-null oocytes indicates an altered DNMT3L localisation, but no change in DNMT1 …
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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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Novel roles of KAT2A chromatin complexes ATAC and SAGA in normal and malignant haematopoiesis
… most part regulated by transcription factors and epigenetic modifiers. The enzymatic activities of epigenetic regulators are of particular importance in malignant haematopoiesis such as leukaemia, given their reversible nature and potential for therapeutic targeting. Epigenetic histone modifiers …
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Investigating the Role of ZNF384 Rearrangements in Acute Leukemia
… partners, most often, transcription factors or epigenetic modifiers. It has been shown that ZNF384-rearranged tumors have a distinct gene expression profile that is consistent between disease groups and N terminal partners. Genomic analyses of patient tumors has shown that ZNF384 fusions arise …
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Creation of Versatile Cloning Platforms for Transgene Expression and Epigenome Editing and Their Application to Pancreatic Islet Biology
… foundation, we also developed an S. aureus dCas9 epigenetic engineering platform, pMAGIC, that enables the packaging of 3 guide RNAs with Sa-dCas9 fused to one of five epigenetic modifiers into a single vector. Using pMAGIC-derived adenoviruses, we functionally validated the regulation of PDX1 by …
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Epigenetic regulation of neuroinflammation in the aged mouse brain
… suggesting that they are a likely target for epigenetic regulation. In order to determine possible causes and targets for interventions to promote healthy aging, the current dissertation explored the role of epigenetic regulation in microglia as well as potential pharmacological and dietary …
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Defining the Epigenetic Evolutionary Dynamics that Precede Acute Myeloid Leukaemia
… well as the ease of sampling blood, mutations in epigenetic modifiers are some of the earliest and most common driver events in AML. In this work, we used peripheral blood samples from a longitudinal cohort of 50 pre-AML donors and 50 age-matched controls (>500 samples overall) to understand the …
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