Bird lab paper featured in Nature Neuroscience. Image Authors 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 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. Related links Journal Link This article was published on 2024-06-17
