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Supervised by: Dr Courtney Hanna (cwh36@cam.ac.uk) and Prof Anne Ferguson-Smith (afsmith@gen.cam.ac.uk) |
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Project Title: The impact of DNA methylation on gene regulation in placental development |
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| Host Department: Department of Physiology, Development and Neuroscience | |
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Project description DNA methylation is an epigenetic modification that exerts its function through the recruitment of epigenetic repressors or interfering with transcription factor binding to silence gene expression. DNA methylation is dramatically reprogrammed during early development in both the embryonic and extra-embryonic lineages. During this reprogramming event, the placental genome only becomes about half as methylated as most other cell types, a feature that is maintained throughout pregnancy and is conserved across mammalian species. Despite this atypical patterning, using transgenic mouse models, we have recently demonstrated that DNA methylation is essential for placental development and function. Yet, it remains unknown which genomic loci are responsive to DNA methylation in the placenta and what changes in gene expression underpin the developmental phenotypes. To address these questions, this PhD project will use multi-omics techniques to identify regulatory elements that become de-repressed upon loss of DNA methylation in placental cells. Using CRISPR epigenetic editting techniques, the impact of region-specific changes in DNA methylation on gene regulation and trophoblast differentiation can then be functionally tested in cultured trophoblast stem cells |
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