Epigenetic Histone Modifications H3K36me3 and H4K5/8/12/16ac Induce Open Polynucleosome Conformations via Different Mechanisms.

Autor: Lin YY; Department of Physics and Center for NanoScience (CeNS), LMU Munich, Amaliensstrasse 54, 80799 Munich, Germany; Soft Condensed Matter and Biophysics, Department of Physics and Debye Institute for Nanomaterials Science, Utrecht University, Princetonplein 1, 3584 CC Utrecht, the Netherlands., Müller P; Department of Physics and Center for NanoScience (CeNS), LMU Munich, Amaliensstrasse 54, 80799 Munich, Germany; Soft Condensed Matter and Biophysics, Department of Physics and Debye Institute for Nanomaterials Science, Utrecht University, Princetonplein 1, 3584 CC Utrecht, the Netherlands., Karagianni E; Soft Condensed Matter and Biophysics, Department of Physics and Debye Institute for Nanomaterials Science, Utrecht University, Princetonplein 1, 3584 CC Utrecht, the Netherlands., Hepp N; Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany; Current address: Department of Clinical Genetics, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark., Mueller-Planitz F; Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307 Dresden, Germany., Vanderlinden W; Department of Physics and Center for NanoScience (CeNS), LMU Munich, Amaliensstrasse 54, 80799 Munich, Germany; Soft Condensed Matter and Biophysics, Department of Physics and Debye Institute for Nanomaterials Science, Utrecht University, Princetonplein 1, 3584 CC Utrecht, the Netherlands; School of Physics and Astronomy, University of Edinburg, James Clerk Maxwell Building, Peter Guthrie Tait Road, Edinburgh EH9 3FD, United Kingdom. Electronic address: Willem.Vanderlinden@ed.ac.uk., Lipfert J; Department of Physics and Center for NanoScience (CeNS), LMU Munich, Amaliensstrasse 54, 80799 Munich, Germany; Soft Condensed Matter and Biophysics, Department of Physics and Debye Institute for Nanomaterials Science, Utrecht University, Princetonplein 1, 3584 CC Utrecht, the Netherlands. Electronic address: J.Lipfert@uu.nl.
Jazyk: angličtina
Zdroj: Journal of molecular biology [J Mol Biol] 2024 Aug 15; Vol. 436 (16), pp. 168671. Date of Electronic Publication: 2024 Jun 20.
DOI: 10.1016/j.jmb.2024.168671
Abstrakt: Nucleosomes are the basic compaction unit of chromatin and nucleosome structure and their higher-order assemblies regulate genome accessibility. Many post-translational modifications alter nucleosome dynamics, nucleosome-nucleosome interactions, and ultimately chromatin structure and gene expression. Here, we investigate the role of two post-translational modifications associated with actively transcribed regions, H3K36me3 and H4K5/8/12/16ac, in the contexts of tri-nucleosome arrays that provide a tractable model system for quantitative single-molecule analysis, while enabling us to probe nucleosome-nucleosome interactions. Direct visualization by AFM imaging reveals that H3K36me3 and H4K5/8/12/16ac nucleosomes adopt significantly more open and loose conformations than unmodified nucleosomes. Similarly, magnetic tweezers force spectroscopy shows a reduction in DNA outer turn wrapping and nucleosome-nucleosome interactions for the modified nucleosomes. The results suggest that for H3K36me3 the increased breathing and outer DNA turn unwrapping seen in mononucleosomes propagates to more open conformations in nucleosome arrays. In contrast, the even more open structures of H4K5/8/12/16ac nucleosome arrays do not appear to derive from the dynamics of the constituent mononucleosomes, but are driven by reduced nucleosome-nucleosome interactions, suggesting that stacking interactions can overrule DNA breathing of individual nucleosomes. We anticipate that our methodology will be broadly applicable to reveal the influence of other post-translational modifications and to observe the activity of nucleosome remodelers.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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