Brahma links the SWI/SNF chromatin-remodeling complex with MeCP2-dependent transcriptional silencing

K. N. Harikrishnan, Baker Medical Research Institute
Maggie Z. Chow, Baker Medical Research Institute
Emma K. Baker, Baker Medical Research Institute
Sharmistha Pal, Ohio State University College of Medicine
Sahar Bassal, Baker Medical Research Institute
Daniella Brasacchio, Baker Medical Research Institute
Li Wang, Ohio State University
Jeff M. Craig, Royal Children's Hospital
Peter L. Jones, University of Massachusetts Medical School
Said Sif, Ohio State University College of Medicine
Assam El-Osta, Baker Medical Research Institute

At the time of publication, Peter Jones was not yet affiliated with the University of Massachusetts Medical School.

Abstract

Transcriptional repression of methylated genes can be mediated by the methyl-CpG binding protein MeCP2. Here we show that human Brahma (Brm), a catalytic component of the SWI/SNF-related chromatin-remodeling complex, associates with MeCP2 in vivo and is functionally linked with repression. We used a number of different molecular approaches and chromatin immunoprecipitation strategies to show a unique cooperation between Brm, BAF57 and MeCP2. We show that Brm and MeCP2 assembly on chromatin occurs on methylated genes in cancer and the gene FMR1 in fragile X syndrome. These experimental findings identify a new role for SWI/SNF in gene repression by MeCP2.