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Nat Neurosci. 2013 Jul;16(7):898-902. doi: 10.1038/nn.3434. Epub 2013 Jun 16.

Rett syndrome mutations abolish the interaction of MeCP2 with the NCoR/SMRT co-repressor.

Author information

1
The Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.

Abstract

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.

PMID:
23770565
PMCID:
PMC3786392
DOI:
10.1038/nn.3434
[Indexed for MEDLINE]
Free PMC Article

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