MeCP2 binds to 5hmc enriched within active genes and accessible chromatin in the nervous system
TLDR
In this paper, a quantitative, genome-wide analysis of 5hmC, 5-methylcytosine (5mC), and gene expression in differentiated CNS cell types in vivo is presented.Abstract:
SUMMARY The high level of 5-hydroxymethylcytosine (5hmC) present in neuronal genomes suggests that mechanisms interpreting 5hmC in the CNS may differ from those present in embryonic stem cells. Here, we present quantitative, genome-wide analysis of 5hmC, 5-methylcytosine (5mC), and gene expression in differentiated CNS cell types in vivo. We report that 5hmC is enriched in active genes and that, surprisingly, strong depletion of 5mC is observed over these regions. The contribution of these epigenetic marks to gene expression depends critically on cell type. We identify methyl-CpG-binding protein 2 (MeCP2) as the major 5hmC-binding protein in the brain and demonstrate that MeCP2 binds 5hmC- and 5mC-containing DNA with similar high affinities. The Rett-syndrome-causing mutation R133C preferentially inhibits 5hmC binding. These findings support a model in which 5hmC and MeCP2 constitute a cell-specific epigenetic mechanism for regulation of chromatin structure and gene expression.read more
Citations
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Epigenomics of Major Depressive Disorders and Schizophrenia: Early Life Decides
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Prenatal Ethanol Exposure and Neocortical Development: A Transgenerational Model of FASD.
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Epigenetic regulation of genomic imprinting from germ line to preimplantation
TL;DR: Recent advancements in understanding of how and when parent‐specific DNA methylation is erased and acquired in the germ line as well as maintained during preimplantation development are reviewed and discussed.
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Accurate measurement of 5-methylcytosine and 5-hydroxymethylcytosine in human cerebellum DNA by oxidative bisulfite on an array (OxBS-array).
Sarah F. Field,Dario Beraldi,Martin Bachman,Sabrina K. Stewart,Stephan Beck,Shankar Balasubramanian +5 more
TL;DR: This work describes the use of oxBS in conjunction with the 450K array (oxBS-array) to analyse 5hmC/5mC in cerebellum DNA and provides a novel method for validating the presence of 5mC at low levels, and highlights some of the pitfalls associated with measuring 5hm C and 5m C.
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The senescent cell epigenome.
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TL;DR: This study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.