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

• Published in: Nature neuroscience Vol. 16; no. 7; pp. 898 - 902
• Main Authors: Lyst, Matthew J, Ekiert, Robert, Ebert, Daniel H, Merusi, Cara, Nowak, Jakub, Selfridge, Jim, Guy, Jacky, Kastan, Nathaniel R, Robinson, Nathaniel D, de Lima Alves, Flavia, Rappsilber, Juri, Greenberg, Michael E, Bird, Adrian
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2013; Nature Publishing Group
• Subjects: 631/208/200; 631/378/1689/1373; 631/378/340; Amino acids; Animal Genetics and Genomics; Animals; Antibodies; Behavioral Sciences; Binding proteins; Biological Techniques; Biomedicine; Brain; Brain - metabolism; Brain - pathology; Cells, Cultured; Chromatin; Disease Models, Animal; DNA methylation; Exploratory Behavior - physiology; Genetic aspects; Green Fluorescent Proteins - genetics; Histone Deacetylases - genetics; Histone Deacetylases - metabolism; Immunoprecipitation; Methyl-CpG-Binding Protein 2 - genetics; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Molecular; Mutation; Mutation - genetics; Neurobiology; Neurosciences; Nuclear Receptor Co-Repressor 1 - genetics; Nuclear Receptor Co-Repressor 1 - metabolism; Nuclear Receptor Co-Repressor 2 - genetics; Nuclear Receptor Co-Repressor 2 - metabolism; Peptides; Properties; Proteins; Repressor proteins; Rett syndrome; Rett Syndrome - genetics; Rett Syndrome - pathology; Rett Syndrome - physiopathology

In this study, the authors show that MeCP2 interacts with the NCoR/SMRT co-repressor complex and that a discrete cluster of Rett syndrome–causing mutations in the C-terminal domain of MeCP2 disrupts this interaction, impairing transcriptional repression. Knock-in mice expressing one of these MeCP2 m...