Defining MeCP2 repressor determinants

Among the activities that are dependent on methylation and histone deacetylation are the ATPase remodelling complexes that alter chromatin accessibility and transcriptional competence. Evidence suggests that methyl‐CpG binding protein 2 (MeCP2)/methyl binding domain proteins (MBD) are involved in the recruitment of co‐repressor complexes and the assembly of chromatin on methylated DNA. However, the precise mechanism of MeCP2 repression on methylated DNA in the context of chromatin has been a hotly debated topic. We have recently demonstrated that human Brahma (hBrm), a catalytic component of the SWI/SNF‐related remodelling complex, associates with MeCP2 in vivo and is functionally linked with repression. These findings present a new paradigm for SWI/SNF function that is relevant to our understanding of MeCP2 mediated transcriptional repression. We present for the first time compelling physical and biochemical evidence for a previously undescribed role of cell‐cycle specific regulators associated with repression. Funded by NHMRC.