1. Cell Biology
  2. Chromosomes and Gene Expression
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HP1α is a chromatin crosslinker that controls nuclear and mitotic chromosome mechanics

  1. Amy R Strom
  2. Ronald J Biggs
  3. Edward J Banigan
  4. Xiaotao Wang
  5. Katherine Chiu
  6. Cameron Herman
  7. Jimena Collado
  8. Feng Yue
  9. Joan C Ritland Politz
  10. Leah J Tait
  11. David Scalzo
  12. Agnes Telling
  13. Mark Groudine
  14. Clifford P Brangwynne
  15. John F Marko
  16. Andrew D Stephens  Is a corresponding author
  1. Princeton University, United States
  2. Northwestern University, United States
  3. Massachusetts Institute of Technology, United States
  4. Feinberg School of Medicine, Northwestern University, United States
  5. University of Massachusetts Amherst, United States
  6. The Fred Hutchinson Cancer Research Center, United States
Research Article
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Cite this article as: eLife 2021;10:e63972 doi: 10.7554/eLife.63972

Abstract

Chromatin, which consists of DNA and associated proteins, contains genetic information and is a mechanical component of the nucleus. Heterochromatic histone methylation controls nucleus and chromosome stiffness, but the contribution of heterochromatin protein HP1α (CBX5) is unknown. We used a novel HP1α auxin-inducible degron human cell line to rapidly degrade HP1α. Degradation did not alter transcription, local chromatin compaction, or histone methylation, but did decrease chromatin stiffness. Single-nucleus micromanipulation reveals that HP1α is essential to chromatin-based mechanics and maintains nuclear morphology, separate from histone methylation. Further experiments with dimerization-deficient HP1αI165E indicate that chromatin crosslinking via HP1α dimerization is critical, while polymer simulations demonstrate the importance of chromatin-chromatin crosslinkers in mechanics. In mitotic chromosomes, HP1α similarly bolsters stiffness while aiding in mitotic alignment and faithful segregation. HP1α is therefore a critical chromatin-crosslinking protein that provides mechanical strength to chromosomes and the nucleus throughout the cell cycle and supports cellular functions.

Data availability

We have provided the RNAseq data sets in the supplemental material as excel files

Article and author information

Author details

  1. Amy R Strom

    Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Ronald J Biggs

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Edward J Banigan

    Institute for Medical Engineering and Science and Department of Physics, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5478-7425
  4. Xiaotao Wang

    Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3531-2157
  5. Katherine Chiu

    Biology Department, University of Massachusetts Amherst, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Cameron Herman

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Jimena Collado

    Department of Molecular Biosciences, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Feng Yue

    Northwestern University, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Joan C Ritland Politz

    Basic Sciences Division, The Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Leah J Tait

    Basic Sciences Division, The Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. David Scalzo

    Basic Sciences Division, The Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Agnes Telling

    Basic Sciences Division, The Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Mark Groudine

    Basic Sciences Division, The Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Clifford P Brangwynne

    Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1350-9960
  15. John F Marko

    Department of Molecular Biosciences, Department of Physics and Astronomy, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Andrew D Stephens

    Biology Department, University of Massachusetts Amherst, Amherst, United States
    For correspondence
    Andrew.stephens@umass.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5474-7845

Funding

National Institutes of Health (U54DK107980)

  • John F Marko

National Institutes of Health (U01DA040583)

  • Mark Groudine

National Institutes of Health (1UM1HG011536)

  • John F Marko
  • Andrew D Stephens

National Institutes of Health (R00GM123195)

  • Andrew D Stephens

National Institutes of Health (U54CA193419)

  • John F Marko

National Institutes of Health (U01 DA040601)

  • Clifford P Brangwynne

Mark Foundation For Cancer Research (Life science research foundation Postdoctoral Fellowship,AWD1006303)

  • Amy R Strom

National Institutes of Health (GM114190)

  • Edward J Banigan

National Institutes of Health (R24DK106766)

  • Feng Yue

National Institutes of Health (1R35GM124820)

  • Feng Yue

National Institutes of Health (R01HG009906)

  • Feng Yue

National Institutes of Health (U01CA200060)

  • Feng Yue

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Geeta J Narlikar, University of California, San Francisco, United States

Publication history

  1. Received: October 12, 2020
  2. Accepted: June 8, 2021
  3. Accepted Manuscript published: June 9, 2021 (version 1)

Copyright

© 2021, Strom 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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Further reading

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