期刊
NEUROSCIENCE LETTERS
卷 711, 期 -, 页码 -出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2019.134403
关键词
DNA methylation; Alzheimer's disease; Promoter DNA hypermethylation
资金
- National Institutes of Health/National Institute on Aging [U01AG049508, U01AG052411, R01AG046170, RF1AG054014, RF1AG057440, R01AG057907]
Recent methylome-wide association studies (MWAS) in humans have solidified the concept that aberrant DNA methylation is associated with Alzheimer's disease (AD). We summarize these findings to improve the understanding of mechanisms governing DNA methylation pertinent to transcriptional regulation, with an emphasis of AD-associated promoter DNA hypermethylation, which establishes an epigenetic barrier for transcriptional activation. By considering brain cell type specific expression profiles that have been published only for non-demented individuals, we detail functional activities of selected neuron, microglia, and astrocyte-enriched genes (AGAP2, DUSP6 and GPR37L1, respectively), which are DNA hypermethylated at promoters in AD. We highlight future directions in MWAS including experimental confirmation, functional relevance to AD, cell type-specific temporal characterization, and mechanism investigation.
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