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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Substantial DNA methylation differences between two major neuronal subtypes in human brain.
Alexey Kozlenkov,Minghui Wang,Panos Roussos,Sergei Rudchenko,Mihaela Barbu,Marina Bibikova,Brandy Klotzle,Andrew J. Dwork,Bin Zhang,Yasmin L. Hurd,Eugene V. Koonin,Michael Wegner,Stella Dracheva +12 more
TL;DR: The findings suggest that functional differences between neuronal subtypes are linked to their epigenetic specification, and regions that are differentially methylated in GABA and GLU neurons were significantly enriched for schizophrenia risk loci.
Journal ArticleDOI
Distinct and overlapping control of 5-methylcytosine and 5-hydroxymethylcytosine by the TET proteins in human cancer cells
Emily L. Putiri,Rochelle L. Tiedemann,Rochelle L. Tiedemann,Joyce J. Thompson,Chunsheng Liu,Thai H. Ho,Jeong Hyeon Choi,Keith D. Robertson +7 more
TL;DR: Novel insight is provided into the division of labor among TET proteins and important connections between TET activity, the chromatin landscape, and gene expression are revealed, suggesting that TETs normally promote 5hmC at these loci.
Journal ArticleDOI
Unlocking epigenetic codes in neurogenesis.
TL;DR: The latest in the understanding of the epigenetic regulation in neurogenesis is reviewed, with a particular focus on newly identified cytosine modifications and their dynamics, along with the perspective for future studies.
Journal ArticleDOI
Dynamic changes in DNA methylation and hydroxymethylation when hES cells undergo differentiation toward a neuronal lineage
Mirang Kim,Young-Kyu Park,Tae-Wook Kang,Sang Hun Lee,Yong-Hee Rhee,Jong-Lyul Park,Hee-Jin Kim,Daeyoup Lee,Doheon Lee,Seon-Young Kim,Yong Sung Kim +10 more
TL;DR: Using an in vitro model system of gradual differentiation of human embryonic stem cells into ventral midbrain-type neural precursor cells and terminally into dopamine neurons, dramatic genome-wide changes in 5 mC and 5 hmC patterns during lineage commitment are observed.
Journal ArticleDOI
Chromatin remodeling inactivates activity genes and regulates neural coding
Yue Yang,Tomoko Yamada,Kelly K. Hill,Martin Hemberg,Naveen C. Reddy,Ha Y. Cho,Arden N. Guthrie,Anna Oldenborg,Shane A. Heiney,Shogo Ohmae,Javier F. Medina,Timothy E. Holy,Azad Bonni +12 more
TL;DR: The findings define an epigenetic mechanism that inactivates activity-dependent transcription and regulates dendrite patterning and sensorimotor encoding in the brain.
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