Structural basis of Yta7 ATPase-mediated nucleosome disassembly

ABSTRACT Yta7 is a novel chromatin remodeler harboring a histone-interacting bromodomain (BRD) and two AAA+ modules. It is not well understood how Yta7 recognizes and unfolds histone H3 to promote nucleosome disassembly for DNA replication. By cryo-EM analysis, we here show that Yta7 assembles a three-tiered hexamer ring with a top spiral, a middle AAA1-tier, and a bottom AAA2-tier. Unexpectedly, the Yta7 BRD stabilizes a four-stranded β-helix termed BRD- interacting motif (BIM) of the largely disordered N-terminal region, and they together assemble the spiral structure on top of the hexamer to engage the nucleosome. We found that the Yta7 BRD lacks key residues involved in acetylated peptide recognition, and as such, it is a noncanonical BRD that does not distinguish the H3 acetylation state, consistent with its role in general DNA replication. Upon nucleosome binding, the BRD/BIM spiral transitions into a flat ring to allow threading of the histone H3 tail into the AAA+ chamber. The H3 peptide is stabilized by the AAA1 pore loops 1 and 2 that spiral around the peptide. Therefore, Yta7 unfolds the nucleosome by pulling on the H3 peptide in a rotary staircase mechanism. Our study sheds light on the nucleosome recognition and unfolding mechanism of Yta7.