ArticleNature neuroscience2025
MeCP2 and non-CG DNA methylation stabilize the expression of long genes that distinguish closely related neuron types.
Article in Nature neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Article
- Gene regulatory mechanisms downstream of DNA methylation.Nature reviews. Genetics · 2026Review
- Early postnatal DNA methylation dynamics define neuronal subtypes and are disrupted by MECP2 loss.bioRxiv : the preprint server for biology · 2026Article
- Long-read sequencing technologies and bioinformatics: a new perspective for decoding DNA methylation modifications.Journal of translational medicine · 2026Review
- Mechanistic Links Between DNA Methylation and Protein Translation and Their Impacts on Brain Development.Biology · 2026Review
- MeCP2 gene dosage-dependent neurodevelopmentally restricted defects arise by aberrant activation of cell fate-determining bivalent genes.Nature communications · 2026Article
- Epigenetic and Transcriptomic Pathways Underlying Animal Models of Cognitive and Psychiatric Disorders: A Scoping Review.Current issues in molecular biology · 2026Review
- From chromosomal protein disorder to chromatin phase separation.Epigenetics & chromatin · 2026Review
- Postnatal conversion of methylcytosine to hydroxymethylcytosine reconfigures the human neuronal epigenome.bioRxiv : the preprint server for biology · 2026Article
- Recent advances in epigenetic therapeutics for Rett syndrome: from mechanisms to clinical trials.Frontiers in behavioral neuroscience · 2026Review
- Single-cell DNA methylation analysis tool Amethyst resolves distinct non-CG methylation patterns in human astrocytes and oligodendrocytes.Communications biology · 2025Article
- Non-CG DNA methylation in animal genomes.Nature genetics · 2025Review
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12 authors.
Funding
Abstract
The diversity of mammalian neurons is delineated by subtle gene expression differences that may require specialized mechanisms to be maintained. Neurons uniquely express the longest genes in the genome and use non-CG DNA methylation (mCA), together with the Rett syndrome protein methyl-CpG-binding protein 2 (MeCP2), to control gene expression. However, whether these distinctive gene structures and molecular machinery regulate neuronal diversity remains unexplored. Here, we use genomic and spatial transcriptomic analyses to show that MeCP2 maintains transcriptomic diversity across closely related neuron types. We uncover differential susceptibility of neuronal populations to MeCP2 loss according to global mCA levels and dissect methylation patterns driving shared and distinct MeCP2 gene regulation. We show that MeCP2 regulates long, mCA-enriched, 'repeatedly tuned' genes, that is, genes differentially expressed between many closely related neuron types, including across spatially distinct, vision-dependent gene programs in the visual cortex. Thus, MeCP2 maintains neuron type-specific gene programs to facilitate cellular diversity in the brain.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.