Abstract
Epigenetic processes are known to play an important role in the regulation of embry-onic development and gene expression. Here we utilise next-generation sequencing and bioinformatics methodologies to investigate the role of epigenetics in two different sys-tems, heart and brain. In heart, the endocardium is a distinct understudied epithelial population of cells that is involved in directing morphogenesis of the myocardium, valve leaflets and trabeculae. We generate whole-genome bisulphite sequencing data for the endocardium and endothelium and compare these data to transcriptomic profiles of these cells. We identify a plethora of differentially expressed genes and differentially methylated genomic regions. Through motif analysis we identify the ETS family of transcriptional activators as likely to play a role in the development of the endocardium.In brain, we investigate the role of the CTCF and cohesin DNA binding factors in imprinted gene expression by performing high depth allele-specific ChIP-seq for these two factors. We develop a novel bioinformatics approach for performing allele-specific mapping of next-generation sequencing reads and we compare our results with existing data for mouse liver and embryonic stem cells. We note that embryonic stem cells have fewer unique CTCF binding sites consistent with their undifferentiated profile. We examine CTCF and cohesin binding in the vicinity of imprinted loci and note that CTCF and/or cohesin bind to a subset of imprinted regions, suggesting a heterogeneous mechanism for imprinting.
Collectively, our studies examine the role of epigenetics and their interplay with tran-scription in two distinct systems and identify a variable role for these processes in gene expression and development.
| Date of Award | 2018 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Rebecca Oakey (Supervisor) & David Grimwade (Supervisor) |