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PLoS Genet. 2017 May 12;13(5):e1006793. doi: 10.1371/journal.pgen.1006793. eCollection 2017 May.

MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences to tune transcription in the mammalian brain.

Author information

1
Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, United Kingdom.
2
School of Informatics, University of Edinburgh, Edinburgh, United Kingdom.
3
Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
4
Department of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, Illinois, United States of America.
5
Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois, United States of America.
6
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas, United States of America.
7
Centre for Translational and Chemical Biology, University of Edinburgh, Edinburgh, United Kingdom.

Abstract

Mutations in the gene encoding the methyl-CG binding protein MeCP2 cause several neurological disorders including Rett syndrome. The di-nucleotide methyl-CG (mCG) is the classical MeCP2 DNA recognition sequence, but additional methylated sequence targets have been reported. Here we show by in vitro and in vivo analyses that MeCP2 binding to non-CG methylated sites in brain is largely confined to the tri-nucleotide sequence mCAC. MeCP2 binding to chromosomal DNA in mouse brain is proportional to mCAC + mCG density and unexpectedly defines large genomic domains within which transcription is sensitive to MeCP2 occupancy. Our results suggest that MeCP2 integrates patterns of mCAC and mCG in the brain to restrain transcription of genes critical for neuronal function.

PMID:
28498846
PMCID:
PMC5446194
DOI:
10.1371/journal.pgen.1006793
[Indexed for MEDLINE]
Free PMC Article

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