1. Chromosomes and Gene Expression
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Aurora-A mediated histone H3 phosphorylation of threonine 118 controls condensin I and cohesin occupancy in mitosis

  1. Candice L Wike
  2. Hillary K Graves
  3. Reva Hawkins
  4. Matthew D Gibson
  5. Michelle B Ferdinand
  6. Tao Zhang
  7. Zhihong Chen
  8. Damien F Hudson
  9. Jennifer J Ottesen
  10. Michael G Poirier
  11. Jill Schumacher
  12. Jessica K Tyler  Is a corresponding author
  1. University of Texas MD Anderson Cancer Center, United States
  2. The Ohio State University, United States
  3. Royal Children's Hospital, Australia
  4. Ohio State University, United States
  5. University of Texas MD Anderson cancer center, United States
  6. Weill Cornell Medicine, United States
Research Article
  • Cited 13
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Cite this article as: eLife 2016;5:e11402 doi: 10.7554/eLife.11402

Abstract

Phosphorylation of histone H3 threonine 118 (H3 T118ph) weakens histone DNA-contacts, disrupting the nucleosome structure. We show that Aurora-A mediated H3 T118ph occurs at pericentromeres and chromosome arms during prophase and is lost upon chromosome alignment. Expression of H3 T118E or H3 T118I (a SIN mutation that bypasses the need for the ATP-dependent nucleosome remodeler SWI/SNF) leads to mitotic problems including defects in spindle attachment, delayed cytokinesis, reduced chromatin packaging, cohesion loss, cohesin and condensin I loss in human cells. In agreement, overexpression of Aurora-A leads to increased H3 T118ph levels, causing cohesion loss, and reduced levels of cohesin and condensin I on chromatin. Normal levels of H3 T118ph are important because it is required for development in fruit flies. We propose that H3 T118ph alters the chromatin structure during specific phases of mitosis to promote timely condensin I and cohesin disassociation, which is essential for effective chromosome segregation.

Article and author information

Author details

  1. Candice L Wike

    Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    No competing interests declared.
  2. Hillary K Graves

    Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    No competing interests declared.
  3. Reva Hawkins

    Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    No competing interests declared.
  4. Matthew D Gibson

    Department of Physics, The Ohio State University, Columbus, United States
    Competing interests
    No competing interests declared.
  5. Michelle B Ferdinand

    Department of Chemistry and Biochemistry, The Ohio State University, Columbus, United States
    Competing interests
    No competing interests declared.
  6. Tao Zhang

    Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia
    Competing interests
    No competing interests declared.
  7. Zhihong Chen

    Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, United States
    Competing interests
    No competing interests declared.
  8. Damien F Hudson

    Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia
    Competing interests
    No competing interests declared.
  9. Jennifer J Ottesen

    Department of Chemistry and Biochemistry, The Ohio State University, Columbus, United States
    Competing interests
    No competing interests declared.
  10. Michael G Poirier

    Department of Physics, Ohio State University, Columbus, United States
    Competing interests
    No competing interests declared.
  11. Jill Schumacher

    Department of Genetics, University of Texas MD Anderson cancer center, Houston, United States
    Competing interests
    No competing interests declared.
  12. Jessica K Tyler

    Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, United States
    For correspondence
    jet2021@med.cornell.edu
    Competing interests
    Jessica K Tyler, Reviewing editor, eLife.

Reviewing Editor

  1. Peter Verrijzer, Erasmus University Medical Center, Netherlands

Publication history

  1. Received: September 9, 2015
  2. Accepted: February 15, 2016
  3. Accepted Manuscript published: February 16, 2016 (version 1)
  4. Version of Record published: March 9, 2016 (version 2)

Copyright

© 2016, Wike 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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