The TFIIH complex is required to establish and maintain mitotic chromosome structure

  1. Julian Haase
  2. Richard Chen
  3. Wesley M Parker
  4. Mary Kate Bonner
  5. Lisa M Jenkins
  6. Alexander E Kelly  Is a corresponding author
  1. National Cancer Institute, United States
  2. The University of Texas Southwestern Medical Center, United States

Abstract

Condensins compact chromosomes to promote their equal segregation during mitosis, but the mechanism of condensin engagement with and action on chromatin is incompletely understood. Here, we show that the general transcription factor TFIIH complex is continuously required to establish and maintain a compacted chromosome structure in transcriptionally silent Xenopus egg extracts. Inhibiting the DNA-dependent ATPase activity of the TFIIH complex subunit XPB rapidly and reversibly induces a complete loss of chromosome structure and prevents the enrichment of condensins I and II, but not topoisomerase II, on chromatin. In addition, inhibiting TFIIH prevents condensation of both mouse and Xenopus nuclei in Xenopus egg extracts, which suggests an evolutionarily conserved mechanism of TFIIH action. Reducing nucleosome density through partial histone depletion restores chromosome structure and condensin enrichment in the absence of TFIIH activity. We propose that the TFIIH complex promotes mitotic chromosome condensation by dynamically altering the chromatin environment to facilitate condensin loading and condensin-dependent loop extrusion.

Data availability

The original files of the full raw unedited gels and blots and figures with the uncropped gels and blots with the relevant bands clearly labelled have been provided as Source Data files.

Article and author information

Author details

  1. Julian Haase

    Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Richard Chen

    Graduate School of Biomedical Sciences, The University of Texas Southwestern Medical Center, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5447-8646
  3. Wesley M Parker

    Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Mary Kate Bonner

    Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Lisa M Jenkins

    Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1245-1338
  6. Alexander E Kelly

    Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, United States
    For correspondence
    alexander.kelly@nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3395-6012

Funding

National Cancer Institute (Intramural Support)

  • Julian Haase
  • Richard Chen
  • Wesley M Parker
  • Mary Kate Bonner
  • Lisa M Jenkins
  • Alexander E Kelly

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 (NCI IACUC) protocol (LBMB-001-1) of the National Cancer Institute, which is an Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC) accredited research facility.

Reviewing Editor

  1. Silke Hauf, Virginia Tech, United States

Publication history

  1. Preprint posted: November 7, 2021 (view preprint)
  2. Received: November 11, 2021
  3. Accepted: March 15, 2022
  4. Accepted Manuscript published: March 16, 2022 (version 1)
  5. Version of Record published: March 25, 2022 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Julian Haase
  2. Richard Chen
  3. Wesley M Parker
  4. Mary Kate Bonner
  5. Lisa M Jenkins
  6. Alexander E Kelly
(2022)
The TFIIH complex is required to establish and maintain mitotic chromosome structure
eLife 11:e75475.
https://doi.org/10.7554/eLife.75475
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