Nucleosome-Chd1 structure and implications for chromatin remodelling.

Abstract

Chromatin remodelling factors change nucleosome positioning and facilitate DNA transcription, replication, and repair1. The conserved remodelling factor Chd12 can shift nucleosomes and induce a regular nucleosome spacing3–5. Chd1 is required for RNA polymerase II passage through nucleosomes6 and for cellular pluripotency7. Chd1 contains the DNA-binding domains SANT and SLIDE, a bilobal motor domain that hydrolyses adenosine triphosphate (ATP), and a regulatory double chromodomain. Here we report the cryo-electron microscopy (cryo-EM) structure of Chd1 from the yeast S. cerevisiae bound to a nucleosome at a resolution of 4.8 Å. Chd1 detaches two turns of DNA from the histone octamer and binds between the two DNA gyres in a state poised for catalysis. The SANT and SLIDE domains contact detached DNA around superhelical location (SHL) -7 of the first DNA gyre. The ATPase motor binds the second DNA gyre at SHL +2 and is anchored to the N-terminal tail of histone H4 as in a recent nucleosome-Snf2 ATPase structure8. Comparison with published results9 reveals that the double chromodomain swings towards nucleosomal DNA at SHL +1, resulting in ATPase closure. The ATPase can then promote translocation of DNA towards the nucleosome dyad, thereby loosening the first DNA gyre and remodelling the nucleosome. Translocation may involve ratcheting of the two lobes of the ATPase, which is trapped in a pre- or post-translocated state in the absence8 or presence, respectively, of transition state-mimicking compounds.