Cited by 303Genetics and Neurodevelopmental DisordersEpigenetics and DNA MethylationGenomics and Chromatin Dynamics

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

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Chen, Lin, Chen, Kaifu, Lavery, Laura A., Baker, Steven Andrew, Shaw, Chad A., Li, Wei, Zoghbi, Huda Y.·2015·Proceedings of the National Academy of Sciences

Abstract

Significance: Decades of research have not deciphered the mechanism by which methyl-CpG binding protein 2 (MeCP2) regulates transcription and why Rett symptoms manifest 1 to 2 y after birth. We hypothesized that the temporal dynamics of MeCP2 binding might provide an answer. We developed mice with an EGFP-tagged MeCP2 allele to identify high-resolution MeCP2 binding profiles in the adult mouse brain. Using genomic binding profiles, methylation maps, and mRNA deep-sequencing data, we found MeCP2 binds to non-CG methylation (mCH, not mCG) to regulate expression of genes altered in mouse models of MeCP2 disorders. These data and the parallel timing of mCH and MeCP2 postnatal accumulation suggest MeCP2 binds mCH as neurons mature to regulate gene expression, offering an explanation for the delayed onset of Rett.

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Crossref · 10.1073/pnas.1505909112

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Authors
Chen, L., Chen, K., Lavery, L. A., Baker, S. A., Shaw, C. A., Li, W., & Zoghbi, H. Y.
Affiliations
  • Texas Children's Hospital (US)
  • Dan L Duncan Comprehensive Cancer Center (US)
  • Department of Molecular and Human Genetics,
  • Howard Hughes Medical Institute (US)
Venue
Proceedings of the National Academy of Sciences
Published
2015-04-13
Volume
112
Issue
17
Pages
5509-5514
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2166288018
Cited by
301
References
31
Citations by year
2026: 20 · 2025: 21 · 2024: 25 · 2023: 20 · 2022: 23 · 2021: 23 · 2020: 28 · 2019: 21 · 2018: 24 · 2017: 38 · 2016: 37 · 2015: 13 · 2014: 1
FWCI
25.51
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Human Genome Research Institute (R01HG007538, HG007538)
  • National Institute of Neurological Disorders and Stroke (T32NS043124, R01NS057819)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD083092, P30HD024064)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
MeCP2, Rett syndrome, non-CG DNA methylation, neuronal gene expression, transcriptional regulation, DNA methylation, brain-derived neurotrophic factor, brain development, delayed symptom onset, epigenetic regulation
MeSH terms
Animals, Disease Models, Animal, DNA, Gene Expression Regulation, Male, Mice, Transgenic, Neurons, Transcription, Genetic, Rett Syndrome, DNA Methylation, Brain-Derived Neurotrophic Factor, Mice, Methyl-CpG-Binding Protein 2

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