MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences to tune transcription in the mammalian brain.
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...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-05-01
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| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006793&type=printable |
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| _version_ | 1849467573617295360 |
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| author | Sabine Lagger John C Connelly Gabriele Schweikert Shaun Webb Jim Selfridge Bernard H Ramsahoye Miao Yu Chuan He Guido Sanguinetti Lawrence C Sowers Malcolm D Walkinshaw Adrian Bird |
| author_facet | Sabine Lagger John C Connelly Gabriele Schweikert Shaun Webb Jim Selfridge Bernard H Ramsahoye Miao Yu Chuan He Guido Sanguinetti Lawrence C Sowers Malcolm D Walkinshaw Adrian Bird |
| author_sort | Sabine Lagger |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-1a9520b92d1044c68c65fae93e056e6c |
| institution | Kabale University |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2017-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-1a9520b92d1044c68c65fae93e056e6c2025-08-20T03:26:10ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042017-05-01135e100679310.1371/journal.pgen.1006793MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences to tune transcription in the mammalian brain.Sabine LaggerJohn C ConnellyGabriele SchweikertShaun WebbJim SelfridgeBernard H RamsahoyeMiao YuChuan HeGuido SanguinettiLawrence C SowersMalcolm D WalkinshawAdrian BirdMutations 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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006793&type=printable |
| spellingShingle | Sabine Lagger John C Connelly Gabriele Schweikert Shaun Webb Jim Selfridge Bernard H Ramsahoye Miao Yu Chuan He Guido Sanguinetti Lawrence C Sowers Malcolm D Walkinshaw Adrian Bird MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences to tune transcription in the mammalian brain. PLoS Genetics |
| title | MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences to tune transcription in the mammalian brain. |
| title_full | MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences to tune transcription in the mammalian brain. |
| title_fullStr | MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences to tune transcription in the mammalian brain. |
| title_full_unstemmed | MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences to tune transcription in the mammalian brain. |
| title_short | MeCP2 recognizes cytosine methylated tri-nucleotide and di-nucleotide sequences to tune transcription in the mammalian brain. |
| title_sort | mecp2 recognizes cytosine methylated tri nucleotide and di nucleotide sequences to tune transcription in the mammalian brain |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006793&type=printable |
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