ISWI catalyzes nucleosome sliding in condensed nucleosome arrays
Nature Structural & Molecular Biology article with first-author IRTG alumna Petra Vizjak (AG Müller-Planitz)
25.04.2024
Petra Vizjak, Dieter Kamp, Nicola Hepp, Alessandro Scacchetti, Mariano Gonzalez Pisfil, Joseph Bartho, Mario Halic, Peter B. Becker,
Michaela Smolle, Johannes Stigler & Felix Mueller-Planitz (2024 Apr 25) ISWI catalyzes nucleosome sliding in condensed nucleosome arrays. Nature Structural & Molecular Biology. https://doi.org/10.1038/s41594-024-01290-x
Abstract cited directly from the article:
How chromatin enzymes work in condensed chromatin and how they maintain diffusional mobility inside remains unexplored. Here we
investigated these challenges using the Drosophila ISWI remodeling ATPase, which slides nucleosomes along DNA. Folding of chromatin fibers did not affect sliding in vitro. Catalytic rates were also comparable in- and outside of chromatin condensates. ISWI cross-links and thereby stiffens condensates, except when ATP hydrolysis is possible. Active hydrolysis is also required for ISWI’s mobility in condensates. Energy from ATP hydrolysis therefore fuels ISWI’s diffusion through chromatin and prevents ISWI from cross-linking chromatin. Molecular dynamics simulations of a ‘monkey-bar’ model in which ISWI grabs onto neighboring nucleosomes, then withdraws from one before rebinding another in an ATP hydrolysis-dependent manner, qualitatively agree with our data. We speculate that monkey-bar mechanisms could be shared with other chromatin factors and that changes in chromatin dynamics caused by mutations in remodelers could contribute to pathologies.