Cross-talk within a functional INO80 complex dimer regulates nucleosome sliding

Abstract

Several chromatin remodellers have the ability to space nucleosomes on DNA. For ISWI remodellers, this involves an interplay between H4 histone tails, the AutoN and NegC motifs of the motor domains that together regulate ATPase activity and sense the length of DNA flanking the nucleosome. By contrast, the INO80 complex also spaces nucleosomes but is not regulated by H4 tails and lacks the AutoN and NegC motifs. Instead nucleosome sliding requires cooperativity between two INO80 complexes that monitor DNA length simultaneously on either side of the nucleosome during sliding. The C-terminal domain of the human Ino80 subunit (Ino80CTD) binds cooperatively to DNA and dimerisation of these domains provides crosstalk between complexes. ATPase activity, rather than being regulated, instead gradually becomes uncoupled as nucleosome sliding reaches an end point and this is controlled by the Ino80CTD. A single active ATPase motor within the dimer is sufficient for sliding.

Article and author information

Author details

  1. Oliver Willhoft

    Section of Structural Biology, Department of Medicine, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Elizabeth A McCormack

    Section of Structural Biology, Department of Medicine, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Ricardo J Aramayo

    Section of Structural Biology, Department of Medicine, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Rohan Bythell-Douglas

    Section of Structural Biology, Department of Medicine, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Lorraine Ocloo

    Section of Structural Biology, Department of Medicine, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Xiaodong Zhang

    Section of Structural Biology, Department of Medicine, Imperial College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9786-7038
  7. Dale B Wigley

    Section of Structural Biology, Department of Medicine, Imperial College London, London, United Kingdom
    For correspondence
    d.wigley@imperial.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0786-6726

Funding

Cancer Research UK (C6913/A21608)

  • Dale B Wigley

Wellcome (095519/Z/11/Z)

  • Dale B Wigley

Wellcome (098412/Z/12/Z)

  • Xiaodong Zhang

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

Reviewing Editor

  1. Jerry L Workman, Stowers Institute for Medical Research, United States

Publication history

  1. Received: February 6, 2017
  2. Accepted: June 3, 2017
  3. Accepted Manuscript published: June 6, 2017 (version 1)
  4. Version of Record published: June 15, 2017 (version 2)

Copyright

© 2017, Willhoft 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. Oliver Willhoft
  2. Elizabeth A McCormack
  3. Ricardo J Aramayo
  4. Rohan Bythell-Douglas
  5. Lorraine Ocloo
  6. Xiaodong Zhang
  7. Dale B Wigley
(2017)
Cross-talk within a functional INO80 complex dimer regulates nucleosome sliding
eLife 6:e25782.
https://doi.org/10.7554/eLife.25782

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