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MeCP2 binds to mCH as neurons mature, influencing transcription and onset of Rett syndrome

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE66871 | GEO | 2015/04/15

SECONDARY ACCESSION(S): PRJNA278140

REPOSITORIES: GEO

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MeCP2 binds to mCH as neurons mature, influencing transcription and onset of Rett syndrome

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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

Project description: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.

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