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Abstract
Chromatin remodellers hydrolyse ATP to move nucleosomal DNA against histone octamers. The mechanism, however, is only partially resolved, and it is unclear if it is conserved among the four remodeller families. Here we use single-molecule assays to examine the mechanism of action of CHD4, which is part of the least well understood family. We demonstrate that the binding energy for CHD4-nucleosome complex formation—even in the absence of nucleotide—triggers significant conformational changes in DNA at the entry side, effectively priming the system for remodelling. During remodelling, flanking DNA enters the nucleosome in a continuous, gradual manner but exits in concerted 4–6 base-pair steps. This decoupling of entry- and exit-side translocation suggests that ATP-driven movement of entry-side DNA builds up strain inside the nucleosome that is subsequently released at the exit side by DNA expulsion. Based on our work and previous studies, we propose a mechanism for nucleosome sliding.
Highlights
Chromatin remodellers hydrolyse ATP to move nucleosomal DNA against histone octamers
We show that CHD4 binding in the absence of nucleotide induces substantial dynamics at the DNA entry side, suggesting that the binding energy of CHD4 alone makes a significant contribution to remodelling
Little was known about the CHD4-driven nucleosome remodelling mechanism
Summary
Chromatin remodellers hydrolyse ATP to move nucleosomal DNA against histone octamers. The “twist diffusion” model proposes that the remodeller changes the structure of the DNA helix, causing a twist defect, and hydrolysis of ATP results in directional transfer of a few base pairs to the adjacent DNA segment[19,20]. Both models hypothesise that the entry site movement happens prior to DNA exiting the nucleosome, a concept that is supported by a recent three-fluorophore smFRET analysis of CHD1 and ISWI activity[21]
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