Published May 12, 2017
| Version v1
Journal article
Open
MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences to tune transcription in the mammalian brain
Creators
- 1. University of Edinburgh
- 2. University of Chicago
- 3. University of Texas
Description
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.
Data availability
All relevant data are within the paper and its Supporting Information files. The next generation sequencing data are available on GEO (https://www.ncbi.nlm.nih.gov/geo/) under accession number GSE84671.
Files
journal.pgen.1006793.pdf
Files
(45.2 MB)
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Article md5:c0415752f45a7013d5d3ff1fcca86ff7 |
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Supporting information md5:bd95af9f0937fd694fe7656877d67d33 |
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Additional details
Identifiers
- DOI
- 10.1371/journal.pgen.1006793
- Other
- oai:uchicago.tind.io:6645
Funding
- The Rett Syndrome Research Trust
- Consortium Grant
- Wellcome Trust
- programme grant
- Wellcome Trust
- Centre Core Grant
- European Research Council
- MLCS 306999
- Unknown funder
- Marie Curie Postdoc fellowship
- University of Vienna
- Veterinary Medicine Postdoc program
- National Cancer Institute
- CA184097