The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription and the timing of onset for Rett syndrome
Open accessAbstract
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“A previous study showed that the binding of MeCP2 to non-CpG methylates DNA sequences is critical for BDNF expression. This process influenced the onset timing for Rett syndrome.64”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [64]
In the citing paper
“In neurons, intragenic 5mCH quantitatively modulates gene expression by interacting with MECP2 and recruiting NCoR corepressor complex to chromatin (37–40).”
From Dynamic DNA methylation: In the right place at the right time (2018) · cites this paper as [38]
Citations
Cites
Initial sequencing and comparative analysis of the mouse genome
Mouse Genome Sequencing Consortium (2002) · Nature · doi:10.1038/nature01262 · Cited by 7,187
Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2
Amir, R. E., Van den Veyver, I. B., Wan, M., Tran, C. Q., Francke, U., & Zoghbi, H. Y. (1999) · Nature Genetics · doi:10.1038/13810 · Cited by 4,990
Self-citationDNA methylation landscapes: Provocative insights from epigenomics
Suzuki, M. M., & Bird, A. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2341 · Cited by 3,039
Methylated DNA and MeCP2 recruit histone deacetylase to repress transcription
Jones, P. L., Veenstra, G. J. C., Wade, P. A., Vermaak, D., Kass, S. U., Landsberger, N., Strouboulis, J., & Wolffe, A. P. (1998) · Nature Genetics · doi:10.1038/561 · Cited by 2,791
Global epigenomic reconfiguration during mammalian brain development
Lister, R., Mukamel, E. A., Nery, J. R., Urich, M., Puddifoot, C. A., Johnson, N. D., Lucero, J., Huang, Y., Dwork, A. J., Schultz, M. D., et al. (2013) · Science · doi:10.1126/science.1237905 · Cited by 1,830
MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription
Chahrour, M., Jung, S. Y., Shaw, C., Zhou, X., Wong, S. T. C., Qin, J., & Zoghbi, H. Y. (2008) · Science · doi:10.1126/science.1153252 · Cited by 1,823
Self-citationA mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome
Guy, J., Hendrich, B., Holmes, M., Martin, J. E., & Bird, A. (2001) · Nature Genetics · doi:10.1038/85899 · Cited by 1,558
Lewis, J. D., Meehan, R. R., Henzel, W. J., Maurer-Fogy, I., Jeppesen, P., Klein, F., & Bird, A. (1992) · Cell · doi:10.1016/0092-8674(92)90610-o · Cited by 1,371
Reversal of Neurological Defects in a Mouse Model of Rett Syndrome
Guy, J., Gan, J., Selfridge, J., Cobb, S., & Bird, A. (2007) · Science · doi:10.1126/science.1138389 · Cited by 1,230
MeCP2 binds to 5hmC enriched within active genes and accessible chromatin in the nervous system
Mellén, M., Ayata, P., Dewell, S., Kriaucionis, S., & Heintz, N. (2012) · Cell · doi:10.1016/j.cell.2012.11.022 · Cited by 943
Flagged first, then by citations
Cited by
Sorted by citations
Items 301–304 of 304
Epigenetic architecture of the developing brain
Moshe Szyf, A. (2026) · Handbook of clinical neurology · doi:10.1016/b978-0-443-19043-8.00022-0
DNA methylation in human disease: From biological mechanisms to clinical applications
Mallik, R., Gupta, P., Gupta, A. K., Chaturvedi, P., Pillai, V., & Muegge, K. (2026) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2026.102635
MeCP2 stabilizes the glucocorticoid system in active chromatin regions
Liu, D., Chen, J., Wang, X., Zhang, X., Wang, R., Yang, L., Rao, X., Zheng, X., Zhou, L., Jiang, M., et al. (2026) · 中国科学通报：英文版 · doi:10.1016/j.scib.2026.10.066
Integration of polygenic risk with single cell methylation data using met-scDRS
Li, X., Shi, Z., Hou, K., Eyring, K. W., Liu, C., Heffel, M. G., Luo, C., Geschwind, D. H., & Pasaniuc, B. (2026) · Bioinformatics · doi:10.1093/bioinformatics/btag751
Metadata
- 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
- Publisher
- National Academy of Sciences
- Published
- 2015-04-13
- Volume
- 112
- Issue
- 17
- Pages
- 5509-5514
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4418849
- 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
- FWCI
- 25.51
- Type
- journal article
- Language
- en
- Update notices
- correction (2015-04-27)
- Open access
- green
- www.ncbi.nlm.nih.gov
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
