Letter | Published:

Nucleosome–Chd1 structure and implications for chromatin remodelling

Nature volume 550, pages 539542 (26 October 2017) | Download Citation

Abstract

Chromatin-remodelling factors change nucleosome positioning and facilitate DNA transcription, replication, and repair1. The conserved remodelling factor chromodomain-helicase-DNA binding protein 1(Chd1)2 can shift nucleosomes and induce regular nucleosome spacing3,4,5. Chd1 is required for the passage of RNA polymerase IIthrough nucleosomes6 and for cellular pluripotency7. Chd1 contains the DNA-binding domains SANT and SLIDE, a bilobal motor domain that hydrolyses ATP, and a regulatory double chromodomain. Here we report the cryo-electron microscopy structure of Chd1 from the yeast Saccharomyces cerevisiae bound to a nucleosome at a resolution of 4.8 Å. Chd1 detaches two turns of DNA from the histone octamer and binds between the two DNA gyres in a state poised for catalysis. The SANT and SLIDE domains contact detached DNA around superhelical location (SHL) −7 of the first DNA gyre. The ATPase motor binds the second DNA gyre at SHL +2 and is anchored to the N-terminal tail of histone H4, as seen in a recent nucleosome–Snf2 ATPase structure8. Comparisons with published results9 reveal that the double chromodomain swings towards nucleosomal DNA at SHL +1, resulting in ATPase closure. The ATPase can then promote translocation of DNA towards the nucleosome dyad, thereby loosening the first DNA gyre and remodelling the nucleosome. Translocation may involve ratcheting of the two lobes of the ATPase, which is trapped in a pre- or post-translocation state in the absence8 or presence, respectively, of transition state-mimicking compounds.

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Acknowledgements

We thank past and present members of the Cramer laboratory including F. Fischer, R. Kohler, S. Neyer, D. Tegunov, and Y. Xu. We thank the members of the Halic laboratory for Xenopus laevis histone expression plasmids, a plasmid containing the Widom 601 sequence and initial advice on histone purification. S.M.V. was supported by an EMBO Long-Term-Fellowship (ALTF 745-2014). P.C. was supported by the Deutsche Forschungsgemeinschaft (SFB860, SPP1935), the European Research Council Advanced Investigator Grant TRANSREGULON (grant agreement No. 693023), and the Volkswagen Foundation.

Author information

Affiliations

  1. Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Am Fassberg 11, 37077 Göttingen, Germany

    • Lucas Farnung
    • , Seychelle M. Vos
    • , Christoph Wigge
    •  & Patrick Cramer

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Contributions

L.F. designed and carried out experiments and performed cryo-EM data acquisition and analysis. S.M.V. developed the protein expression strategy, performed baculovirus production, and insect cell expression. C.W. assisted with cryo-EM grid preparation and data collection. P.C. designed and supervised research. L.F. and P.C. interpreted the data and wrote the manuscript, with input from all authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Patrick Cramer.

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Extended data

Supplementary information

PDF files

  1. 1.

    Supplementary Figure 1

    This file contains the uncropped scan with size marker indication. The region presented in Extended Data Figure 1a is indicated by rectangle with dashed lines.

  2. 2.

    Reporting Summary

Videos

  1. 1.

    Overview of the nucleosome-Chd1 structure

    A 3D overview of the nucleosome-Chd1 structure fitted into the cryo-EM electron density.

  2. 2.

    Structural changes and ATPase activation

    The video first shows DNA detachment, then swinging of the double chromodomain onto nucleosomal DNA, and then ATPase closure.

  3. 3.

    Model for DNA translocation by the Chd1 ATPase motor

    The video shows a model for DNA translocation by the Chd1 ATPase motor on B-DNA. For details see text.

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DOI

https://doi.org/10.1038/nature24046

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