Structure of SWI/SNF chromatin remodeler RSC bound to a nucleosome

Chromatin remodelling complexes of the SWI/SNF family function in the formation of nucleosome-depleted, transcriptionally active promoter regions (NDRs)(1,2). The essential Saccharomyces cerevisiae SWI/SNF complex RSC(3) contains 16 subunits, including the ATP-dependent DNA translocase Sth1(4,5). RSC removes nucleosomes from promoter regions(6,7) and positions the specialized +1 and –1 nucleosomes that flank NDRs(8,9). Here, we present the cryo-EM structure of RSC in complex with a nucleosome substrate. The structure reveals that RSC forms five protein modules and suggests key features of the remodelling mechanism. The body module serves as a scaffold for the four flexible modules that we call DNA-interacting, ATPase, arm and ARP modules. The DNA-interacting module binds extra-nucleosomal DNA and is involved in the recognition of promoter DNA elements(8,10,11) that influence RSC functionality(12). The ATPase and arm modules sandwich the nucleosome disc with their ‘SnAC’ and ‘finger’ elements, respectively. The translocase motor of the ATPase module engages with the edge of the nucleosome at superhelical location +2. The mobile ARP module may modulate translocase-nucleosome interactions to regulate RSC activity(5). The RSC-nucleosome structure provides a basis for understanding NDR formation and the structure and function of human SWI/SNF complexes that are frequently mutated in cancer(13).