SWI/SNF (BAF) Complexes: Guardians of the Epigenome

Abstract

The genomics-era search for cancer-causing mutations has identified subunits of SWI/SNF (BAF) chromatin remodeling complexes as major targets of mutation. The mechanism by which mutations in SWI/SNF complexes might drive cancer has become the subject of debate, as these complexes have roles in both transcriptional regulation and maintenance of genomic integrity. Recent discoveries now reveal that SWI/SNF complexes broadly control the activity of transcriptional enhancers to regulate lineage-specific differentiation. Here, we synthesize an integrative model of SWI/SNF complex function, identifying perturbed control of enhancer activity as the central mechanism underlying tumor suppression and highlighting how this yields new opportunities for therapeutic intervention.