Concerted regulation of ISWI by an autoinhibitory domain and the H4 N-terminal tail

  1. Johanna Ludwigsen
  2. Sabrina Pfennig
  3. Ashish K Singh
  4. Christina Schindler
  5. Nadine Harrer
  6. Ignasi Forné
  7. Martin Zacharias
  8. Felix Mueller-Planitz  Is a corresponding author
  1. Ludwig-Maximilians-Universität München, Germany
  2. Technische Universität München, Germany

Abstract

ISWI-family nucleosome remodeling enzymes need the histone H4 N-terminal tail to mobilize nucleosomes. Here we mapped the H4-tail binding pocket of ISWI. Surprisingly the binding site was adjacent to but not overlapping with the docking site of an auto-regulatory motif, AutoN, in the N-terminal region (NTR) of ISWI, indicating that AutoN does not act as a simple pseudosubstrate as suggested previously. Rather, AutoN cooperated with a hitherto uncharacterized motif, termed AcidicN, to confer H4-tail sensitivity and discriminate between DNA and nucleosomes. A third motif in the NTR, ppHSA, was functionally required in vivo and provided structural stability by clamping the NTR to Lobe 2 of the ATPase domain. This configuration is reminiscent of Chd1 even though Chd1 contains an unrelated NTR. Our results shed light on the intricate structural and functional regulation of ISWI by the NTR and uncover surprising parallels with Chd1.

Article and author information

Author details

  1. Johanna Ludwigsen

    Biomedical Center, Ludwig-Maximilians-Universität München, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Sabrina Pfennig

    Biomedical Center, Ludwig-Maximilians-Universität München, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Ashish K Singh

    Biomedical Center, Ludwig-Maximilians-Universität München, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Christina Schindler

    Biomedical Center, Ludwig-Maximilians-Universität München, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Nadine Harrer

    Biomedical Center, Ludwig-Maximilians-Universität München, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Ignasi Forné

    Biomedical Center, Ludwig-Maximilians-Universität München, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Martin Zacharias

    Physics Department, Technische Universität München, Garching, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Felix Mueller-Planitz

    Biomedical Center, Ludwig-Maximilians-Universität München, Martinsried, Germany
    For correspondence
    felix.mueller-planitz@med.uni-muenchen.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8273-6473

Funding

Ernst Schering Foundation

  • Johanna Ludwigsen

Deutscher Akademischer Austauschdienst

  • Ashish K Singh

Deutsche Forschungsgemeinschaft (CIPSM)

  • Martin Zacharias

Deutsche Forschungsgemeinschaft (MU 3613/1-1 MU 3613/3-1 SFB 1064/1TP-A07)

  • Felix Mueller-Planitz

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: September 13, 2016
  2. Accepted: January 20, 2017
  3. Accepted Manuscript published: January 21, 2017 (version 1)
  4. Version of Record published: February 13, 2017 (version 2)

Copyright

© 2017, Ludwigsen 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. Johanna Ludwigsen
  2. Sabrina Pfennig
  3. Ashish K Singh
  4. Christina Schindler
  5. Nadine Harrer
  6. Ignasi Forné
  7. Martin Zacharias
  8. Felix Mueller-Planitz
(2017)
Concerted regulation of ISWI by an autoinhibitory domain and the H4 N-terminal tail
eLife 6:e21477.
https://doi.org/10.7554/eLife.21477

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