Chromatin remodelers couple inchworm motion with twist-defect formation to slide nucleosomal DNA

by Giovanni B. Brandani, Shoji Takada ATP-dependent chromatin remodelers are molecular machines that control genome organization by repositioning, ejecting, or editing nucleosomes, activities that confer them essential regulatory roles on gene expression and DNA replication. Here, we investigate the molecular mechanism of active nucle osome sliding by means of molecular dynamics simulations of the Snf2 remodeler translocase in complex with a nucleosome. During its inchworm motion driven by ATP consumption, the translocase overwrites the original nucleosome energy landscape via steric and electrostatic interactions to induce slidi ng of nucleosomal DNA unidirectionally. The sliding is initiated at the remodeler binding location via the generation of a pair of twist defects, which then spontaneously propagate to complete sliding throughout the entire nucleosome. We also reveal how remodeler mutations and DNA sequence control a ctive nucleosome repositioning, explaining several past experimental observations. These results offer a detailed mechanistic picture of remodeling important for the complete understanding of these key biological processes.
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research