ArticleeLife2014
Rett-causing mutations reveal two domains critical for MeCP2 function and for toxicity in MECP2 duplication syndrome mice.
Article in eLife, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 99 citations in OpenAlex.
- Programmable CRISPRtune dissects the transcriptional repressive activity of MeCP2.bioRxiv : the preprint server for biology · 2026Article
- From Gene to Hope: Rett Syndrome and the Rise of Molecular Therapies.Molecular diagnosis & therapy · 2026Review
- MeCP2 requires interactions with nucleosome linker DNA to read chromatin DNA methylation.Nature communications · 2026Article
- Early differential impact of MeCP2 mutations on functional networks in Rett syndrome patient-derived human cortical organoids.Nature communications · 2026Article
- Antisense oligonucleotides to KIF1A polymorphisms expand targets and rescue patient-derived neurons in vitro.Nature communications · 2026Article
- Immunomodulation of behavior impairment via spleen-specific targeting lipid nanoparticles in a MeCP2 transgenic mouse model.Scientific reports · 2025Article
- Comprehensive in Silico Reclassification of MECP2 Variants of Uncertain Significance in Rett Syndrome: Performance Evaluation and Structural Analysis.Journal of molecular neuroscience : MN · 2025Article
- MECP2 Dysfunction in Rett Syndrome: Molecular Mechanisms, Multisystem Pathology, and Emerging Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Precise in vivo RNA base editing with a wobble-enhanced circular CLUSTER guide RNA.Nature biotechnology · 2025Article
- An RNA editing strategy rescues gene duplication in a mouse model of MECP2 duplication syndrome and nonhuman primates.Nature neuroscience · 2025Article
- Article
- Epigenetic Regulation and Neurodevelopmental Disorders: From MeCP2 to the TCF20/PHF14 Complex.Genes · 2024Review
- Site-blocking antisense oligonucleotides as a mechanism to fine-tune MeCP2 expression.RNA (New York, N.Y.) · 2024Article
- Differential dynamics specify MeCP2 function at nucleosomes and methylated DNA.Nature structural & molecular biology · 2024Article
- MeCP2 gene therapy ameliorates disease phenotype in mouse model for Pitt Hopkins syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- An Irak1-Mecp2 tandem duplication mouse model for the study of MECP2 duplication syndrome.Disease models & mechanisms · 2024Article
- MeCP2 represses the activity of topoisomerase IIβ in long neuronal genes.Cell reports · 2023Article
- Analysis of the interplay between MeCP2 and histone H1 duringEpigenetics · 2023Article
- A novel pathogenic mutation of MeCP2 impairs chromatin association independent of protein levels.Genes & development · 2023Article
- Novel MECP2 gene therapy is effective in a multicenter study using two mouse models of Rett syndrome and is safe in non-human primates.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
8 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
Loss of function of the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2) causes the progressive neurological disorder Rett syndrome (RTT). Conversely, duplication or triplication of Xq28 causes an equally wide-ranging progressive neurological disorder, MECP2 duplication syndrome, whose features overlap somewhat with RTT. To understand which MeCP2 functions cause toxicity in the duplication syndrome, we generated mouse models expressing endogenous Mecp2 along with a RTT-causing mutation in either the methyl-CpG binding domain (MBD) or the transcriptional repression domain (TRD). We determined that both the MBD and TRD must function for doubling MeCP2 to be toxic. Mutating the MBD reproduces the null phenotype and expressing the TRD mutant produces milder RTT phenotypes, yet both mutations are harmless when expressed with endogenous Mecp2. Surprisingly, mutating the TRD is more detrimental than deleting the entire C-terminus, indicating a dominant-negative effect on MeCP2 function, likely due to the disruption of a basic cluster.
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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.