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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Affinity for DNA Contributes to NLS Independent Nuclear Localization of MeCP2.
Matthew J. Lyst,Robert Ekiert,Jacky Guy,Jim Selfridge,Martha V. Koerner,Cara Merusi,Dina De Sousa,Adrian Bird +7 more
TL;DR: It is reported that nuclear localization of MeCP2 does not depend on its NLS, and an intact methyl-CpG binding domain (MBD) is sufficient for nuclear localization, suggesting that Me CP2 can be retained in the nucleus by its affinity for DNA.
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DNA recognition of 5-carboxylcytosine by a Zfp57 mutant at an atomic resolution of 0.97 Å.
TL;DR: Structurally, it is shown that the uncharged amide group of E182Q interacts favorably with the carboxylate group of 5caC, and introducing a positively charged arginine at position 182 resulted in a mutant (E182R) having higher selectivity for the negatively charged5caC.
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L1 retrotransposition is activated by Ten-eleven-translocation protein 1 and repressed by methyl-CpG binding proteins.
Peng Zhang,Anne K. Ludwig,Florian D. Hastert,Cathia Rausch,Anne Lehmkuhl,Ines Hellmann,Martha Smets,Heinrich Leonhardt,M. Cristina Cardoso +8 more
TL;DR: It is demonstrated that the methyl-CpG binding domain, as well as the adjacent non-sequence specific DNA binding domain of Mecp2 are each sufficient to mediate repression of Tet1-induced L1 mobilization.
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