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
Citations
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Formation of cyclobutane pyrimidine dimers at dipyrimidines containing 5-hydroxymethylcytosine
TL;DR: It is shown that the formation of CPDs at dipyrimidines containing 5hmC occurs at different DNA sequences but is not enhanced relative to cytosine or 5-methylcytosines at the same sequence positions.
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Methyl-CpG Binding Protein 2 (MeCP2) Localizes at the Centrosome and Is Required for Proper Mitotic Spindle Organization
Anna Bergo,Marta Strollo,Marta Gai,Isabella Barbiero,Gilda Stefanelli,Sarah Sertic,Clementina Cobolli Gigli,Ferdinando Di Cunto,Charlotte Kilstrup-Nielsen,Nicoletta Landsberger,Nicoletta Landsberger +10 more
TL;DR: A novel MeCP2 phospho-isoform (Tyr-120) whose relevance was suggested by a Rett syndrome patient carrying a Y120D substitution possibly mimicking a constitutively phosphorylated state is characterized and found at the centrosome both in dividing and postmitotic cells.
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Cerebral organoids as tools to identify the developmental roots of autism.
TL;DR: It is suggested that cerebral organoids, in their current form, are most suitable to model earlier neurodevelopmental events and processes such as neurogenesis and cortical lamination which occur at later stages of development.
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The distinct methylation landscape of maturing neurons and its role in Rett syndrome pathogenesis.
Laura A. Lavery,Huda Y. Zoghbi +1 more
TL;DR: The current understanding of RTT, the landscape of pathogenic mutations and function of MeCP2, and recent advances elucidating the distinct DNA methylation landscape in the brain that may explain why disease symptoms are delayed and selective to the nervous system are reviewed.
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The histone demethylase Kdm6b regulates a mature gene expression program in differentiating cerebellar granule neurons.
Ranjula Wijayatunge,Fang Liu,Karl B. Shpargel,Nicole J. Wayne,Urann Chan,Jane Valeriane Boua,Terry Magnuson,Anne E. West +7 more
TL;DR: Data reveal a previously unknown role for KDM6b in the postmitotic stages of CGN maturation and suggest that Kdm6b may work, at least in part, by a transcriptional mechanism that promotes gene sensitivity to regulation by BDNF.
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