ArticleThe Journal of biological chemistry2008
Rett syndrome-causing mutations in human MeCP2 result in diverse structural changes that impact folding and DNA interactions.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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48 citing papers in PubMed, 72 citations in OpenAlex.
- Structures of MeCP2 bound to nucleosomes reveal distinct mechanisms of Rett syndrome mutations.bioRxiv : the preprint server for biology · 2026Article
- DNA methylation, nucleic acid structure, and rett mutations tune MeCP2 binding affinity and cooperativity.The Journal of biological chemistry · 2026Article
- MeCP2 requires interactions with nucleosome linker DNA to read chromatin DNA methylation.Nature communications · 2026Article
- Metformin Treatment Shows Beneficial Effects on RTT-Associated Phenotypical Deficits inPharmaceuticals (Basel, Switzerland) · 2026Article
- Genetic Traces in Autism Spectrum Disorders: A Whole Exome Sequencing Study from Türkiye.Genes · 2026Article
- Comprehensive in Silico Reclassification of MECP2 Variants of Uncertain Significance in Rett Syndrome: Performance Evaluation and Structural Analysis.Journal of molecular neuroscience : MN · 2025Article
- Human MeCP2 binds to promoters and inhibits transcription in an unmethylated yeast genome.Genetics · 2025Article
- Article
- Epigenetic control of adaptive or homeostatic splicing during interval-training activities.Nucleic acids research · 2024Article
- Genetics behind Cerebral Disease with Ocular Comorbidity: Finding Parallels between the Brain and Eye Molecular Pathology.International journal of molecular sciences · 2022Review
- Profiling beneficial and potential adverse effects of MeCP2 overexpression in a hypomorphic Rett syndrome mouse model.Genes, brain, and behavior · 2022Article
- Rett Syndrome andNeuropsychiatric disease and treatment · 2022Review
- Stabilization Effect of Intrinsically Disordered Regions on Multidomain Proteins: The Case of the Methyl-CpG Protein 2, MeCP2.Biomolecules · 2021Article
- A catalogue of 863 Rett-syndrome-causing MECP2 mutations and lessons learned from data integration.Scientific data · 2021Article
- MeCP2: The Genetic Driver of Rett Syndrome Epigenetics.Frontiers in genetics · 2021Review
- Molecular Context-Dependent Effects Induced by Rett Syndrome-Associated Mutations in MeCP2.Biomolecules · 2020Article
- Rett syndrome-causing mutations compromise MeCP2-mediated liquid-liquid phase separation of chromatin.Cell research · 2020Article
- Genomic insights into MeCP2 function: A role for the maintenance of chromatin architecture.Current opinion in neurobiology · 2019Review
- Leveraging the genetic basis of Rett syndrome to ascertain pathophysiology.Neurobiology of learning and memory · 2019Review
- Readers of DNA methylation, the MBD family as potential therapeutic targets.Pharmacology & therapeutics · 2018Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Most cases of Rett syndrome (RTT) are caused by mutations in the methylated DNA-binding protein, MeCP2. Here, we have shown that frequent RTT-causing missense mutations (R106W, R133C, F155S, T158M) located in the methylated DNA-binding domain (MBD) of MeCP2 have profound and diverse effects on its structure, stability, and DNA-binding properties. Fluorescence spectroscopy, which reports on the single tryptophan in the MBD, indicated that this residue is strongly protected from the aqueous environment in the wild type but is more exposed in the R133C and F155S mutations. In the mutant proteins R133C, F155S, and T158M, the thermal stability of the domain was strongly reduced. Thermal stability of the wild-type protein was increased in the presence of unmethylated DNA and was further enhanced by DNA methylation. DNA-induced thermal stability was also seen, but to a lesser extent, in each of the mutant proteins. Circular dichroism (CD) of the MBD revealed differences in the secondary structure of the four mutants. Upon binding to methylated DNA, the wild type showed a subtle but reproducible increase in alpha-helical structure, whereas the F155S and R106W did not acquire secondary structure with DNA. Each of the mutant proteins studied is unique in terms of the properties of the MBD and the structural changes induced by DNA binding. For each mutation, we examined the extent to which the magnitude of these differences correlated with the severity of RTT patient symptoms.
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