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Neuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state.

TitleNeuronal MeCP2 is expressed at near histone-octamer levels and globally alters the chromatin state.
Publication TypeJournal Article
Year of Publication2010
AuthorsSkene PJ, Illingworth R, Webb S, Kerr ARW, James KD, Turner DJ, Andrews R, Bird AP
JournalMol Cell
Date Published2010 Feb 26
KeywordsAnimals, Brain, Cell Nucleus, Chromatin, CpG Islands, DNA Methylation, Genome, Histones, Methyl-CpG-Binding Protein 2, Mice, Mice, Inbred C57BL, Mice, Knockout, Neurons, Nucleosomes, Protein Binding, Protein Multimerization, Transcription, Genetic

MeCP2 is a nuclear protein with an affinity for methylated DNA that can recruit histone deacetylases. Deficiency or excess of MeCP2 causes severe neurological problems, suggesting that the number of molecules per cell must be precisely regulated. We quantified MeCP2 in neuronal nuclei and found that it is nearly as abundant as the histone octamer. Despite this high abundance, MeCP2 associates preferentially with methylated regions, and high-throughput sequencing showed that its genome-wide binding tracks methyl-CpG density. MeCP2 deficiency results in global changes in neuronal chromatin structure, including elevated histone acetylation and a doubling of histone H1. Neither change is detectable in glia, where MeCP2 occurs at lower levels. The mutant brain also shows elevated transcription of repetitive elements. Our data argue that MeCP2 may not act as a gene-specific transcriptional repressor in neurons, but might instead dampen transcriptional noise genome-wide in a DNA methylation-dependent manner.

Alternate JournalMol. Cell
PubMed ID20188665
PubMed Central IDPMC4338610
Grant List077224 / / Wellcome Trust / United Kingdom
079643 / / Wellcome Trust / United Kingdom
/ / Wellcome Trust / United Kingdom
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