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Title: | DNA METHYLATION DYNAMICS AND EPIGENETIC MEMORY IN HIGHLY METABOLIC MAMMALIAN ORGANS | Authors: | JAIME OLIVER PITFIELD WORSLEY | Keywords: | Epigenetic memory, Heart Failure, NAFLD, DNA methylation, reversibility | Issue Date: | 26-Jan-2018 | Citation: | JAIME OLIVER PITFIELD WORSLEY (2018-01-26). DNA METHYLATION DYNAMICS AND EPIGENETIC MEMORY IN HIGHLY METABOLIC MAMMALIAN ORGANS. ScholarBank@NUS Repository. | Abstract: | Differences in the mammalian epigenome are mostly lost between generations, henceforth dramatic changes in the epigenome occur during development which confer cellular identity and specificity. However, environmental influences further remodels the epigenome and can produce long lasting memory. The mammalian liver and heart are highly metabolic organs that are subject to environmental stresses. After evaluating different models of cardiac remodelling and liver stress, we found clear DNA methylation signatures in both organs unique to stress conditions. A major finding in the heart was a hypomethylated mitochondrial gene persisting long after chronic exercise, and this primed its upregulation in the setting of heart failure leading to excessive apoptosis, inflammation and fibrosis. The clinical relevance for these findings is clear, where we might be able to one day prevent the persistent memories that aggravate the response to subsequent pathological events. | URI: | http://scholarbank.nus.edu.sg/handle/10635/145425 |
Appears in Collections: | Ph.D Theses (Open) |
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