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

Matthew J. Lyst, Robert Ekiert, Daniel H. Ebert, Cara Merusi, Jakub Nowak, Jim Selfridge, Jacky Guy, Nathaniel R. Kastan, Nathaniel D. Robinson, Flavia De Lima Alves, Juri Rappsilber, Michael E. Greenberg, Adrian Bird

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)898-902
Number of pages5
JournalNature neuroscience
Volume16
Issue number7
DOIs
StatePublished - Jul 2013
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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