ISWI catalyzes nucleosome sliding in condensed nucleosome arrays.


Journal

Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374

Informations de publication

Date de publication:
25 Apr 2024
Historique:
received: 03 11 2022
accepted: 25 03 2024
medline: 26 4 2024
pubmed: 26 4 2024
entrez: 25 4 2024
Statut: aheadofprint

Résumé

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.

Identifiants

pubmed: 38664566
doi: 10.1038/s41594-024-01290-x
pii: 10.1038/s41594-024-01290-x
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Auteurs

Petra Vizjak (P)

Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Department of Molecular Biology, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.
Early Stage Bioprocess Development, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.

Dieter Kamp (D)

Gene Center, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.

Nicola Hepp (N)

Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Department of Molecular Biology, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.
Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Alessandro Scacchetti (A)

Department of Molecular Biology, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.
Epigenetics Institute and Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Mariano Gonzalez Pisfil (M)

Core Facility Bioimaging and Walter-Brendel-Centre of Experimental Medicine, Biomedical Center, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.

Joseph Bartho (J)

Gene Center, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany.
European Molecular Biology Laboratory, Heidelberg, Germany.

Mario Halic (M)

Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Peter B Becker (PB)

Department of Molecular Biology, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.

Michaela Smolle (M)

Department of Physiological Chemistry, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.
BioPhysics Core Facility, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-Universität München, Planegg-Martinsried, Germany.
ViraTherapeutics GmbH, Rum, Austria.

Johannes Stigler (J)

Gene Center, Department of Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany. stigler@genzentrum.lmu.de.

Felix Mueller-Planitz (F)

Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany. felix.mueller-planitz@tu-dresden.de.

Classifications MeSH