MeCP2 binds to 5hmc enriched within active genes and accessible chromatin in the nervous system
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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
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Shaping synaptic plasticity: the role of activity-mediated epigenetic regulation on gene transcription.
TL;DR: It is described how Ca2+ entry through N‐methyl‐d‐aspartate‐type glutamate neurotransmitter receptors result in the activation of specific signaling pathways leading to changes in gene expression, giving special emphasis to the recent data pointing out different epigenetic mechanisms underlying learning and memory.
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Region-specific RNA m6A methylation represents a new layer of control in the gene regulatory network in the mouse brain
Mengqi Chang,Hongyi Lv,Hongyi Lv,Weilong Zhang,Chunhui Ma,Xue He,Shunli Zhao,Zhi Wei Zhang,Yi-Xin Zeng,Shuhui Song,Yamei Niu,Wei-Min Tong +11 more
TL;DR: The results imply that RNA m6A methylation is a newly identified element in the region-specific gene regulatory network in the mouse brain, and is likely to be used for selective recognition of target mRNAs by FMRP in the synapse.
Journal ArticleDOI
Rett syndrome and MeCP2
TL;DR: A synopsis of Rett syndrome as a severe neurological disorder and the role of MeCP2 in RTT pathophysiology is discussed, which highlights the importance of understanding the molecular mechanisms by which Me CP2 impacts brain development, mental conditions, and compromised brain function.
Journal ArticleDOI
The role of epigenetic mechanisms in the regulation of gene expression in the nervous system
Justyna Cholewa-Waclaw,Adrian Bird,Melanie J. von Schimmelmann,Anne Schaefer,Huimei Yu,Hongjun Song,Ram Madabhushi,Li-Huei Tsai +7 more
TL;DR: A selective review of the role of DNA and histone modifications in neuronal signal-induced gene expression regulation, plasticity, and survival and how targeting these mechanisms could advance the development of future therapies is provided.
Journal ArticleDOI
TET3 is recruited by REST for context-specific hydroxymethylation and induction of gene expression.
Arshan Perera,David Eisen,Mirko Wagner,Silvia K. Laube,Andrea F. Künzel,Susanne Koch,Jessica Steinbacher,E. Schulze,Victoria Splith,Nana Mittermeier,Markus Müller,Martin Biel,Thomas Carell,Stylianos Michalakis +13 more
TL;DR: A mechanism for transcriptional activation in neurons is proposed that involves REST-guided targeting of TET3 to the DNA for directed 5hmC generation and NSD3-mediated H3K36 trimethylation.
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