1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
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Nucleosome-CHD4 chromatin remodeller structure maps human disease mutations

  1. Lucas Farnung  Is a corresponding author
  2. Moritz Ochmann
  3. Patrick Cramer  Is a corresponding author
  1. Max Planck Institute for Biophysical Chemistry, Germany
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Cite this article as: eLife 2020;9:e56178 doi: 10.7554/eLife.56178

Abstract

Chromatin remodelling plays important roles in gene regulation during development, differentiation and in disease. The chromatin remodelling enzyme CHD4 is a component of the NuRD and ChAHP complexes that are involved in gene repression. Here we report the cryo-electron microscopy (cryo-EM) structure of Homo sapiens CHD4 engaged with a nucleosome core particle in the presence of the non-hydrolysable ATP analogue AMP-PNP at an overall resolution of 3.1 Å. The ATPase motor of CHD4 binds and distorts nucleosomal DNA at superhelical location (SHL) +2, supporting the 'twist defect' model of chromatin remodelling. CHD4 does not induce unwrapping of terminal DNA, in contrast to its homologue Chd1, which functions in gene activation. Our structure also maps CHD4 mutations that are associated with human cancer or the intellectual disability disorder Sifrim-Hitz-Weiss syndrome.

Article and author information

Author details

  1. Lucas Farnung

    Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    For correspondence
    Lucas.Farnung@mpibpc.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8200-2493
  2. Moritz Ochmann

    Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Patrick Cramer

    Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
    For correspondence
    patrick.cramer@mpibpc.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5454-7755

Funding

Deutsche Forschungsgemeinschaft (SFB1064)

  • Patrick Cramer

Deutsche Forschungsgemeinschaft (SFB860)

  • Patrick Cramer

European Research Council (693023)

  • Patrick Cramer

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: March 10, 2020
  2. Accepted: June 15, 2020
  3. Accepted Manuscript published: June 16, 2020 (version 1)

Copyright

© 2020, Farnung 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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