CHD4 slides nucleosomes by decoupling entry- and exit-side DNA translocation

• DOI: 10.1038/s41467-020-15183-2
• Publication Date: 2020-03-23T11:03:40Z
• Authors: Yichen Zhong; Bishnu P. Paudel; Daniel P. Ryan; Jason K. K. Low; Charlotte Franck; Karishma Patel; Max J. Bedward; Mario Torrado; Richard J. Payne; Antoine M. van Oijen; Joel P. Mackay
• Keywords: 0303 health sciences; Saccharomyces cerevisiae Proteins; Intravital Microscopy; Science; Q; 612; Chromatin Assembly and Disassembly; Article; Recombinant Proteins; Single Molecule Imaging; Translocation, Genetic; Nucleosomes; DNA-Binding Proteins; Histones; 03 medical and health sciences; HEK293 Cells; Microscopy, Fluorescence; Protein Domains; Humans; Mi-2 Nucleosome Remodeling and Deacetylase Complex

Abstract Chromatin remodellers hydrolyse ATP to move nucleosomal DNA against histone octamers. The mechanism, however, is only partially resolved, and it unclear if conserved among the four remodeller families. Here we use single-molecule assays examine mechanism of action CHD4, which part least well understood family. We demonstrate that binding energy for CHD4-nucleosome complex formation—even in absence nucleotide—triggers significant conformational changes at entry side, effectively priming system remodelling. During remodelling, flanking enters nucleosome a continuous, gradual manner but exits concerted 4–6 base-pair steps. This decoupling entry- exit-side translocation suggests ATP-driven movement entry-side builds up strain inside subsequently released exit side by expulsion. Based on our work previous studies, propose sliding.