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

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. Overall design: RNA-seq in Mouse Embryonic Fibroblasts in WT condition and for knockouts of different SWI/SNF complex subunits.

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Alver BH, Kim KH, Lu P, Wang X, Manchester HE, Wang W, Haswell JR, Park PJ, Roberts CW