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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DNA Methylation in Nonalcoholic Fatty Liver Disease.
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TL;DR: An update on the recent findings in DNA methylation signatures and their roles in the pathogenesis of NAFLD is reviewed and people’s perspectives on potentialDNA methylation-related treatments and biomarkers forNAFLD are broadened.
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Epigenetics of Sleep and Chronobiology
Irfan A. Qureshi,Mark F. Mehler +1 more
TL;DR: Attention is drawn to the fundamental roles played by epigenetic mechanisms in transcriptional and post-transcriptional regulation within the circadian clock system and how alterations in epigenetic factors and mechanisms are being linked with sleep-wake disorders.
Journal ArticleDOI
New themes in the biological functions of 5-methylcytosine and 5-hydroxymethylcytosine.
Erika L. Moen,Christopher J. Mariani,Hayley Zullow,Meselle Jeff-Eke,Edward Litwin,John N. Nikitas,Lucy A. Godley +6 more
TL;DR: The functions of 5‐mC and 5‐hmC at distinct genic contexts are discussed, including promoter regions, gene bodies, intron‐exon boundaries, alternative promoters, and intragenic microRNAs, and their functions at enhancers and transcription factor binding sites.
Journal ArticleDOI
Leptin resistance and obesity in mice with deletion of methyl-CpG-binding protein 2 (MeCP2) in hypothalamic pro-opiomelanocortin (POMC) neurons
TL;DR: In vitro studies show that hypermethylation of the Pomc promoter reduces its transcriptional activity and reveal a functional synergy between MeCP2 and cAMP responsive element binding protein 1 (CREB1) in positively regulating the PomC promoter.
Journal ArticleDOI
MECP2 Is a Frequently Amplified Oncogene with a Novel Epigenetic Mechanism that Mimics the Role of Activated RAS in Malignancy
Manish Neupane,Allison P. Clark,Serena Landini,Nicolai Juul Birkbak,Aron Charles Eklund,Elgene Lim,Aedín C. Culhane,William T. Barry,Steven E. Schumacher,Rameen Beroukhim,Zoltan Szallasi,Marc Vidal,David E. Hill,Daniel P. Silver +13 more
TL;DR: Observations suggest that MECP2 is a commonly amplified oncogene with an unusual epigenetic mode of action in human malignancies with a unique epigenetic mechanism of action.
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