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

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.

SUBMITTER: Lyst MJ 

PROVIDER: S-EPMC3786392 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature