An RNA binding module of SWI/SNF is required for activation of cell-type specific enhancers and super-enhancers in early development

Abstract

AbstractThe mammalian SWI/SNF complex is an ATP-dependent chromatin remodeler and master regulator in development that when mutated is the cause for several human diseases including cancer. Although SWI/SNF is highly enriched at enhancers and its basic chromatin remodeling activities have been studied for over 30 years, there is little known about how it regulates enhancer activity or enhancer-promoter interactions. We find a putative RNA binding module located near the C-terminus of the catalytic subunit of SWI/SNF required for SWI/SNF recruitment to cell-type specific enhancers and super-enhancers in naïve and cell lineage primed pluripotent cells. The AT-hook is required for acquisition of the active histone marks H3K27ac and H3K4me1 and recruitment of the MLL3/4 co-activator to these enhancers and super-enhancers. Consistent with changes in enhancer architecture, loss of the AT-hook interferes with activation of genes involved in cell lineage priming as well as genes normally activated in naïve pluripotent cells.