Choppakatla, P. orcid.org/0000-0003-0387-913X, Dekker, B., Cutts, E.E. orcid.org/0000-0003-3290-4293 et al. (3 more authors) (2021) Linker histone H1.8 inhibits chromatin binding of condensins and DNA topoisomerase II to tune chromosome length and individualization. eLife, 10. e68918. ISSN 2050-084X
Abstract
DNA loop extrusion by condensins and decatenation by DNA topoisomerase II (topo II) are thought to drive mitotic chromosome compaction and individualization. Here, we reveal that the linker histone H1.8 antagonizes condensins and topo II to shape mitotic chromosome organization. In vitro chromatin reconstitution experiments demonstrate that H1.8 inhibits binding of condensins and topo II to nucleosome arrays. Accordingly, H1.8 depletion in <jats:italic>Xenopus</jats:italic> egg extracts increased condensins and topo II levels on mitotic chromatin. Chromosome morphology and Hi-C analyses suggest that H1.8 depletion makes chromosomes thinner and longer through shortening the average loop size and reducing the DNA amount in each layer of mitotic loops. Furthermore, excess loading of condensins and topo II to chromosomes by H1.8 depletion causes hyper-chromosome individualization and dispersion. We propose that condensins and topo II are essential for chromosome individualization, but their functions are tuned by the linker histone to keep chromosomes together until anaphase.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 The Authors. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Hi-C; chromatin; chromosome compaction; chromosomes; gene expression; linker histone; mitosis; nucleosome; xenopus; Adenosine Triphosphatases; Animals; Cell Extracts; Chromatin; Chromosomes; DNA Topoisomerases, Type II; DNA-Binding Proteins; Female; Histones; Models, Biological; Multiprotein Complexes; Oocytes; Spindle Apparatus; Xenopus laevis |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 23 Jan 2025 10:49 |
Last Modified: | 23 Jan 2025 10:49 |
Published Version: | https://doi.org/10.7554/elife.68918 |
Status: | Published |
Publisher: | eLife Sciences Publications, Ltd |
Refereed: | Yes |
Identification Number: | 10.7554/elife.68918 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:221963 |