ArticleNature2017
Radically truncated MeCP2 rescues Rett syndrome-like neurological defects.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 2 of them syntheses that pooled it.
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Who cites it
98 citing papers in PubMed, 2 syntheses or guidelines pooled it, 158 citations in OpenAlex.
- Evidence Synthesis of Gene Therapy and Gene Editing from Different Disorders-Implications for Individuals with Rett Syndrome: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Autonomic dysfunction and sudden death in patients with Rett syndrome: a systematic reviewJournal of psychiatry & neuroscience : JPN · 2020Pooled it
- MeCP2 MBD-ID module: a unified DNA/RNA binding interface disrupted in Rett syndrome.Nucleic acids research · 2026Article
- Translational reading frame predicts the pathogenicity of C-terminal frameshift deletions in MeCP2.eLife · 2026Article
- From Gene to Hope: Rett Syndrome and the Rise of Molecular Therapies.Molecular diagnosis & therapy · 2026Review
- Neural peer pressure: intercellular dynamics and emergent phenotypes in the mosaic Rett syndrome brain.Cell communication and signaling : CCS · 2026Review
- Dysfunction of a SET3-like complex underlies a family of related neurological disorders.Nature communications · 2026Article
- MeCP2 gene dosage-dependent neurodevelopmentally restricted defects arise by aberrant activation of cell fate-determining bivalent genes.Nature communications · 2026Article
- MeCP2 requires interactions with nucleosome linker DNA to read chromatin DNA methylation.Nature communications · 2026Article
- MeCP2 NID interaction with RNA: implications for Rett syndrome-relevant protein regulation.Human molecular genetics · 2026Article
- Cell-Penetrating Peptides and Supercharged Proteins: A Comprehensive Protocol from Isolation to Cellular Uptake.Molecular pharmaceutics · 2026Article
- Translational reading frame determines the pathogenicity of C-terminal frameshift deletions in MeCP2: an alternative therapeutic approach.bioRxiv : the preprint server for biology · 2025Article
- Advancing precision diagnosis in autism: Insights from large-scale genomic studies.Molecules and cells · 2025Review
- Effects of Ionizing Radiation on DNA Methylation Patterns and Their Potential as Biomarkers.International journal of molecular sciences · 2025Review
- Article
- Interaction of methyl-CpG-binding protein 2 (MeCP2) with distinct enhancers in the mouse cortex.Nature neuroscience · 2025Article
- Preclinical Milestones in MECP2 Gene Transfer for Treating Rett Syndrome.Developmental neuroscience · 2025Review
- Rett syndrome: interferon-γ to the rescue?EMBO molecular medicine · 2024Article
- Article
- Rett syndrome.Nature reviews. Disease primers · 2024Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Heterozygous mutations in the X-linked MECP2 gene cause the neurological disorder Rett syndrome. The methyl-CpG-binding protein 2 (MeCP2) protein is an epigenetic reader whose binding to chromatin primarily depends on 5-methylcytosine. Functionally, MeCP2 has been implicated in several cellular processes on the basis of its reported interaction with more than 40 binding partners, including transcriptional co-repressors (for example, the NCoR/SMRT complex), transcriptional activators, RNA, chromatin remodellers, microRNA-processing proteins and splicing factors. Accordingly, MeCP2 has been cast as a multi-functional hub that integrates diverse processes that are essential in mature neurons. At odds with the concept of broad functionality, missense mutations that cause Rett syndrome are concentrated in two discrete clusters coinciding with interaction sites for partner macromolecules: the methyl-CpG binding domain and the NCoR/SMRT interaction domain. Here we test the hypothesis that the single dominant function of MeCP2 is to physically connect DNA with the NCoR/SMRT complex, by removing almost all amino-acid sequences except the methyl-CpG binding and NCoR/SMRT interaction domains. We find that mice expressing truncated MeCP2 lacking both the N- and C-terminal regions (approximately half of the native protein) are phenotypically near-normal; and those expressing a minimal MeCP2 additionally lacking a central domain survive for over one year with only mild symptoms. This minimal protein is able to prevent or reverse neurological symptoms when introduced into MeCP2-deficient mice by genetic activation or virus-mediated delivery to the brain. Thus, despite evolutionary conservation of the entire MeCP2 protein sequence, the DNA and co-repressor binding domains alone are sufficient to avoid Rett syndrome-like defects and may therefore have therapeutic utility.
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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.