Structural insights into assembly and function of the RSC chromatin remodeling complex

Chromatin remodelers regulate the position and composition of nucleosomes throughout the genome, producing different remodeling outcomes despite a shared underlying mechanism based on a conserved RecA DNA translocase. How this functional diversity is achieved remains unknown despite recent cryo-electron microscopy (cryo-EM) reconstructions of several remodelers, including the yeast RSC complex. To address this, we have focused on a RSC subcomplex comprising its ATPase (Sth1), the essential actin-related proteins (ARPs) Arp7 and Arp9, and the fungal-specific protein Rtt102. Combining cryo-EM and biochemistry of this subcomplex, which exhibits regulation of remodeling by the ARPs, we show that ARP binding induces a helical conformation in the HSA domain of Sth1, which bridges the ATPase domain with the bulk of the complex. Surprisingly, the ARP module is rotated by 120{degrees} in the subcomplex relative to full RSC about a pivot point previously identified as a regulatory hub in Sth1, suggesting that large conformational changes are part of Sth1 regulation and RSC assembly. We also show that an interaction between Sth1 and the nucleosome acidic patch, which appears to be conserved among SWI/SNF remodelers, enhances remodeling. Taken together, our structural data shed light on the assembly and function of the RSC complex.