Linker histone H1.8 inhibits chromatin-binding of condensins and DNA topoisomerase II to tune chromosome length and individualization
- The Rockefeller University, United States
- University of Massachusetts Medical School, United States
- The Institute of Cancer Research, United Kingdom
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 Xenopus 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.
Data availability
Hi-C sequencing data have been deposited in GEO under an accession code GSE164434.All other data generated or analyzed during this study are included in the manuscript and supporting source data files.
Article and author information
Author details
Funding
National Institutes of Health (R35 GM132111)
- Hironori Funabiki
National Institutes of Health (R01 HG003143)
- Job Dekker
Cancer Research UK (CR-UK C47547/A21536)
- Alessandro Vannini
Wellcome Trust (200818/Z/16/Z)
- Alessandro Vannini
Howard Hughes Medical Institute (Investigator Program)
- Job Dekker
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Adèle L Marston, University of Edinburgh, United Kingdom
Ethics
Animal experimentation: This study was performed in strict accordance with the care standards provided by the 8th edition of the Guide for the Care and Use of Laboratory Animals. African clawed frogs, Xenopus laevis, which were maintained and handled according to approved institutional animal care and use committee (IACUC) protocol (20031) of the Rockefeller University, which is an Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC) accredited research facility.
Version history
- Received: March 30, 2021
- Accepted: August 13, 2021
- Accepted Manuscript published: August 18, 2021 (version 1)
- Accepted Manuscript updated: August 19, 2021 (version 2)
- Version of Record published: September 3, 2021 (version 3)
- Version of Record updated: September 14, 2021 (version 4)
Copyright
© 2021, Choppakatla et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Linker histone H1.8 inhibits chromatin-binding of condensins and DNA topoisomerase II to tune chromosome length and individualization
eLife 10:e68918.
https://doi.org/10.7554/eLife.68918
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