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

Publication Type	Academic Article
Authors	Lyst M, Ekiert R, Ebert D, Merusi C, Nowak J, Selfridge J, Guy J, Kastan N, Robinson N, de Lima Alves F, Rappsilber J, Greenberg M, Bird A
Journal	Nat Neurosci
Volume	16
Issue	7
Pagination	898-902
Date Published	06/16/2013
ISSN	1546-1726
Keywords	Methyl-CpG-Binding Protein 2, Mutation, Nuclear Receptor Co-Repressor 1, Nuclear Receptor Co-Repressor 2, Rett Syndrome
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.
DOI	10.1038/nn.3434
PubMed ID	23770565
PubMed Central ID	PMC3786392