1. Chromosomes and Gene Expression

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
https://doi.org/10.7554/eLife.11402
Share this article
Cite this article
  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
(2016)
Aurora-A mediated histone H3 phosphorylation of threonine 118 controls condensin I and cohesin occupancy in mitosis
eLife 5:e11402.
https://doi.org/10.7554/eLife.11402
  2. Download BibTeX
  3. Download .RIS

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.

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.

Metrics

  • 3,281
    views
  • 885
    downloads
  • 24
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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
(2016)
Aurora-A mediated histone H3 phosphorylation of threonine 118 controls condensin I and cohesin occupancy in mitosis
eLife 5:e11402.
https://doi.org/10.7554/eLife.11402

Share this article

https://doi.org/10.7554/eLife.11402

Categories and tags

Research organisms

Further reading

    1. Chromosomes and Gene Expression
    2. Evolutionary Biology

    The domesticated transposon protein L1TD1 associates with its ancestor L1 ORF1p to promote LINE-1 retrotransposition

    Gülnihal Kavaklioglu, Alexandra Podhornik ... Christian Seiser
    Research Article

    Repression of retrotransposition is crucial for the successful fitness of a mammalian organism. The domesticated transposon protein L1TD1, derived from LINE-1 (L1) ORF1p, is an RNA-binding protein that is expressed only in some cancers and early embryogenesis. In human embryonic stem cells, it is found to be essential for maintaining pluripotency. In cancer, L1TD1 expression is highly correlative with malignancy progression and as such considered a potential prognostic factor for tumors. However, its molecular role in cancer remains largely unknown. Our findings reveal that DNA hypomethylation induces the expression of L1TD1 in HAP1 human tumor cells. L1TD1 depletion significantly modulates both the proteome and transcriptome and thereby reduces cell viability. Notably, L1TD1 associates with L1 transcripts and interacts with L1 ORF1p protein, thereby facilitating L1 retrotransposition. Our data suggest that L1TD1 collaborates with its ancestral L1 ORF1p as an RNA chaperone, ensuring the efficient retrotransposition of L1 retrotransposons, rather than directly impacting the abundance of L1TD1 targets. In this way, L1TD1 might have an important role not only during early development but also in tumorigenesis.

    1. Chromosomes and Gene Expression

    Nuclear Argonaute protein NRDE-3 switches small RNA partners during embryogenesis to mediate temporal-specific gene regulatory activity

    Shihui Chen, Carolyn Marie Phillips
    Research Article

    RNA interference (RNAi) is a conserved pathway that utilizes Argonaute proteins and their associated small RNAs to exert gene regulatory function on complementary transcripts. While the majority of germline-expressed RNAi proteins reside in perinuclear germ granules, it is unknown whether and how RNAi pathways are spatially organized in other cell types. Here, we find that the small RNA biogenesis machinery is spatially and temporally organized during Caenorhabditis elegans embryogenesis. Specifically, the RNAi factor, SIMR-1, forms visible concentrates during mid-embryogenesis that contain an RNA-dependent RNA polymerase, a poly-UG polymerase, and the unloaded nuclear Argonaute protein, NRDE-3. Curiously, coincident with the appearance of the SIMR granules, the small RNAs bound to NRDE-3 switch from predominantly CSR-class 22G-RNAs to ERGO-dependent 22G-RNAs. NRDE-3 binds ERGO-dependent 22G-RNAs in the somatic cells of larvae and adults to silence ERGO-target genes; here we further demonstrate that NRDE-3-bound, CSR-class 22G-RNAs repress transcription in oocytes. Thus, our study defines two separable roles for NRDE-3, targeting germline-expressed genes during oogenesis to promote global transcriptional repression, and switching during embryogenesis to repress recently duplicated genes and retrotransposons in somatic cells, highlighting the plasticity of Argonaute proteins and the need for more precise temporal characterization of Argonaute-small RNA interactions.

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Transcription: The plusses and minuses of DNA torsion

    Steven Henikoff, David L Levens
    Insight

    A new method for mapping torsion provides insights into the ways that the genome responds to the torsion generated by RNA polymerase II.