Rett syndrome mutations abolish the interaction of MeCP2 with the NCoR/SMRT co-repressor
| Autor: | Robert Ekiert, Nathaniel D. Robinson, Daniel H. Ebert, Jim Selfridge, Nathaniel R. Kastan, Cara Merusi, Michael E. Greenberg, Juri Rappsilber, Jacky Guy, Jakub Stanislaw Nowak, Flavia de Lima Alves, Matthew J. Lyst, Adrian Bird |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Models
Molecular congenital hereditary and neonatal diseases and abnormalities Methyl-CpG-Binding Protein 2 Green Fluorescent Proteins Mice Transgenic Rett syndrome Biology medicine.disease_cause Histone Deacetylases Article MECP2 Mice mental disorders Rett Syndrome medicine Animals Immunoprecipitation Nuclear Receptor Co-Repressor 1 Missense mutation Nuclear Receptor Co-Repressor 2 Cells Cultured Nuclear receptor co-repressor 1 Nuclear receptor co-repressor 2 Genetics Mutation General Neuroscience Brain medicine.disease Molecular biology Phenotype nervous system diseases Chromatin Mice Inbred C57BL Disease Models Animal Exploratory Behavior |
| Zdroj: | Nature Neuroscience. 16:898-902 |
| ISSN: | 1546-1726 1097-6256 |
| DOI: | 10.1038/nn.3434 |
| Popis: | Rett syndrome (RTT) is a severe neurological disorder that is caused by mutations in the MECP2 gene. Many missense mutations causing RTT are clustered in the DNA-binding domain of MeCP2, suggesting that association with chromatin is critical for its function. We identified a second mutational cluster in a previously uncharacterized region of MeCP2. We found that RTT mutations in this region abolished the interaction between MeCP2 and the NCoR/SMRT co-repressor complexes. Mice bearing a common missense RTT mutation in this domain exhibited severe RTT-like phenotypes. Our data are compatible with the hypothesis that brain dysfunction in RTT is caused by a loss of the MeCP2 ‘bridge’ between the NCoR/SMRT co-repressors and chromatin. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|