SWR1C catalyzes H2A.Z deposition by coupling ATPase activity to the nucleosome acidic patch
The SWR1C chromatin remodeling enzyme catalyzes the ATP-dependent exchange of nucleosomal histone H2A for the histone variant H2A.Z, a key variant involved in a multitude of nuclear functions. How the 14-subunit SWR1C engages the nucleosomal substrate remains largely unknown. Numerous studies on the ISWI, CHD1, and SWI/SNF families of chromatin remodeling enzymes have demonstrated an essential role for the nucleosomal acidic patch for remodeling activity, however a role for this nucleosomal epitope in nucleosome editing by SWR1C has not been tested. Here, we employ a variety of biochemical assays to demonstrate an essential role for the nucleosomal acidic patch in the H2A.Z exchange reaction. Nucleosomes lacking acidic patch residues retain the ability to stimulate the ATPase activity of SWR1C, implicating a role in coupling the energy of ATP hydrolysis to H2A/H2B dimer eviction. A conserved arginine-rich region within the Swc5 subunit is identified that interacts with the acidic patch and is found to be essential for dimer exchange activity. Together these findings provide new insights into how SWR1C engages its nucleosomal substrate to promote efficient H2A.Z deposition.