Unknown,Transcriptomics,Genomics,Proteomics

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MeCP2 binds to mCH as neurons mature, influencing transcription and onset of Rett syndrome [Mnase-Seq]


ABSTRACT: The postnatal neurodevelopmental disorder Rett syndrome (RTT) is caused by mutations in the gene encoding Methyl-CpG-binding Protein 2 (MeCP2). Despite decades of research, it remains unclear how MeCP2 actually regulates transcription or why RTT features appear only 6-18 months after birth. We examined MeCP2 binding to methylated cytosine in the CH context (mCH, where H = A, C, or T) in the adult mouse brain and found that MeCP2 binds these mCH sites, influencing nucleosome positioning and transcription. Strikingly, this pattern is unique to the mature nervous system, as it requires the increase in mCH after birth to reveal differences in MeCP2 binding to mCG, mCH, and non-methylated DNA elements. This study provides insight into the molecular mechanism governing MeCP2 targeting and how this targeting might contribute to the delayed onset of RTT symptoms. Mnase-Seq were conducted from 7-week-old hypothalamus from MeCP2 knockout mice and their age and genetic background matched wild types control mice.

ORGANISM(S): Mus musculus

SUBMITTER: kaifu chen 

PROVIDER: E-GEOD-66869 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription and the timing of onset for Rett syndrome.

Chen Lin L   Chen Kaifu K   Lavery Laura A LA   Baker Steven Andrew SA   Shaw Chad A CA   Li Wei W   Zoghbi Huda Y HY  

Proceedings of the National Academy of Sciences of the United States of America 20150413 17


Epigenetic mechanisms, such as DNA methylation, regulate transcriptional programs to afford the genome flexibility in responding to developmental and environmental cues in health and disease. A prime example involving epigenetic dysfunction is the postnatal neurodevelopmental disorder Rett syndrome (RTT), which is caused by mutations in the gene encoding methyl-CpG binding protein 2 (MeCP2). Despite decades of research, it remains unclear how MeCP2 regulates transcription or why RTT features app  ...[more]

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