ARID1A regulates histone octamer transfer activity of human canonical BAF complex.

Mutations that impact subunits of mammalian SWI/SNF (mSWI/SNF or BAF) chromatin remodeling complexes are found in over 20% of human cancers. Among these subunits, AT-rich interactive domain-containing protein 1A (ARID1A) is the most frequently mutated gene, occurring in over 8% of various cancers. The majority of ARID1A mutations are frameshift or nonsense mutations, causing loss of function. Previous studies have suggested that ARID1A may facilitate interactions between BAF complexes and various transcriptional coactivators, but a biochemical role for ARID1A in BAF remodeling activity has not been identified. Here, we describe the in vitro reconstitution of the cBAF, PBAF, and ncBAF complexes, and we compare their biochemical activities. In addition, we reconstitute a variety of cBAF subcomplexes, defining roles for several subunits in high affinity nucleosome binding and nucleosome sliding activity. Remarkably, we find that the ARID1A subunit of cBAF is largely dispensable for nucleosome binding, nucleosome sliding, and adenosine triphosphatase activity, but ARID1A is required for cBAF to transfer histone octamers between DNA templates. Our study reveals a biochemical function of ARID1A/ARID1B in BAF-mediated chromatin remodeling, suggesting a model in which dysregulation of histone octamer transfer activity of BAF complexes may be relevant to cancer formation.