The SWI/SNF chromatin remodeling complex is required for lineage specific enhancer activity [MEF_ChIP]

Genes encoding subunits of SWI/SNF (BAF) chromatin remodeling complexes are collectively altered in over 20% of all human malignancies, but the mechanisms by which these complexes alter chromatin to modulate transcription and control cell fate are poorly understood. Utilizing both loss-of-function and gain-of-function approaches, here we show that SWI/SNF complexes are preferentially targeted to distal enhancers and interact with p300 to regulate transcription via modulation of histone H3 lysine 27 acetylation. We identify a greater requirement for SWI/SNF at typical enhancers than at most super-enhancers and at enhancers in untranscribed regions than in transcribed regions. Our data further demonstrate that SWI/SNF-dependent distal enhancers are essential for controlling expression of genes linked to developmental processes. Our findings thus establish SWI/SNF complexes as regulators of the enhancer landscape and provide insight into the roles of SWI/SNF in cellular fate control. ChIP-seq of three histone modifications (H3K27ac, H3K4m3, H3K4me1) and two SWI/SNF complex subunits SMARCC1 and SMARCC4) in WT, Smarcb1-KO and Smarca4-KO Mouse Embryonic Fibroblasts.