1. Chromosomes and Gene Expression

Linker histone H1.8 inhibits chromatin-binding of condensins and DNA topoisomerase II to tune chromosome length and individualization

  1. Pavan Choppakatla
  2. Bastiaan Dekker
  3. Erin E Cutts
  4. Alessandro Vannini
  5. Job Dekker
  6. Hironori Funabiki  Is a corresponding author
  1. The Rockefeller University, United States
  2. University of Massachusetts Medical School, United States
  3. The Institute of Cancer Research, United Kingdom
https://doi.org/10.7554/eLife.68918
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Cite this article
  1. Pavan Choppakatla
  2. Bastiaan Dekker
  3. Erin E Cutts
  4. Alessandro Vannini
  5. Job Dekker
  6. Hironori Funabiki
(2021)
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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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.

The following data sets were generated

Article and author information

Author details

  1. Pavan Choppakatla

    Laboratory of Chromosome and Cell Biology, The Rockefeller University, New York, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0387-913X

  2. Bastiaan Dekker

    Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    No competing interests declared.

  3. Erin E Cutts

    Division of Structural Biology, The Institute of Cancer Research, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3290-4293

  4. Alessandro Vannini

    Division of Structural Biology, The Institute of Cancer Research, London, United Kingdom
    Competing interests
    No competing interests declared.

  5. Job Dekker

    Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    Job Dekker, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5631-0698

  6. Hironori Funabiki

    Laboratory of Chromosome and Cell Biology, The Rockefeller University, New York, United States
    For correspondence
    funabih@rockefeller.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4831-4087

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.

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.

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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  1. Pavan Choppakatla
  2. Bastiaan Dekker
  3. Erin E Cutts
  4. Alessandro Vannini
  5. Job Dekker
  6. Hironori Funabiki
(2021)
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

Share this article

https://doi.org/10.7554/eLife.68918

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