Abstract
As superfamily 2 (SF2)-type translocases, chromatin remodelers are expected to use an inchworm-type mechanism to walk along DNA. Yet how they move DNA around the histone core has not been clear. Here we show that a remodeler ATPase motor can shift large segments of DNA by changing the twist and length of nucleosomal DNA at superhelix location 2 (SHL2). Using canonical and variant 601 nucleosomes, we find that the Saccharomyces cerevisiae Chd1 remodeler decreased DNA twist at SHL2 in nucleotide-free and ADP-bound states, and increased twist with transition state analogs. These differences in DNA twist allow the open state of the ATPase to pull in ~1 base pair (bp) by stabilizing a small DNA bulge, and closure of the ATPase to shift the DNA bulge toward the dyad. We propose that such formation and elimination of twist defects underlie the mechanism of nucleosome sliding by CHD-, ISWI-, and SWI/SNF-type remodelers.
Highlights
Chromatin remodelers are members of the extensive superfamily 2 (SF2) group of ATPase motors found in all kingdoms of life (Flaus and Owen-Hughes, 2001; Flaus et al, 2006)
We identified the arrangement of Chd1 domains on the nucleosome using site-specific cross-linking with 4-azidophenacyl bromide (APB) (Nodelman et al, 2017)
Chd1(V721C) cross-links 19 nt from the dyad and is not directly affected by the sequence changes from swapping the 24–39 segment. These results suggest that the stability or dynamics of the ATPase motor at superhelix location 2 (SHL2) is affected by the sequence of the 24–39 bp segment of the nucleosome
Summary
Chromatin remodelers are members of the extensive superfamily 2 (SF2) group of ATPase motors found in all kingdoms of life (Flaus and Owen-Hughes, 2001; Flaus et al, 2006). SF2 ATPases possess a bi-lobed architecture, with a central ATP-binding pocket defined by two RecA-like domains (reviewed in Singleton et al, 2007). Like the architecturally similar SF1 ATPases, both lobes of the motor coordinate in binding to DNA or RNA, with conformational changes driven by cycles of ATP binding and hydrolysis enabling many SF2 enzymes to translocate in an inchworm fashion along nucleic acids (Singleton et al, 2007). Several chromatin remodelers have been shown to ratchet DNA past the histone core in single bp steps, known as nucleosome sliding, which is consistent with the basic inchworm mechanism of DNA translocation (Deindl et al, 2013; Harada et al, 2016)
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