Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome

  1. Ramasubramanian Sundaramoorthy
  2. Amanda L Hughes
  3. Hassane El-Mkami
  4. David G Norman
  5. Helder Ferreira
  6. Tom Owen-Hughes  Is a corresponding author
  1. University of Dundee, United Kingdom
  2. University of St Andrews, United Kingdom

Abstract

ATP-dependent chromatin remodelling proteins represent a diverse family of proteins that share ATPase domains that are adapted to regulate protein-DNA interactions. Here we present structures of the Saccharomyces cerevisiae Chd1 protein engaged with nucleosomes in the presence of the transition state mimic ADP-beryllium fluoride. The path of DNA strands through the ATPase domains indicates the presence of contacts conserved with single strand translocases and additional contacts with both strands that are unique to Snf2 related proteins. The structure provides connectivity between rearrangement of ATPase lobes to a closed, nucleotide bound state and the sensing of linker DNA. Two turns of linker DNA are prised off the surface of the histone octamer as a result of Chd1 binding, and both the histone H3 tail and ubiquitin conjugated to lysine 120 are re-orientated towards the unravelled DNA. This indicates how changes to nucleosome structure can alter the way in which histone epitopes are presented.

Data availability

The EM structures generated have been deposited in EMDB and PDB under the accession codes EMD-4318, PDB 6FTX, EMD-4336, PDB 6G0L.

The following data sets were generated

Article and author information

Author details

  1. Ramasubramanian Sundaramoorthy

    Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Amanda L Hughes

    Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Hassane El-Mkami

    School of Physics and Astronomy, University of St Andrews, St Andrews, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. David G Norman

    Nucelic Acids Structure Research Group, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7658-7720
  5. Helder Ferreira

    School of Biology, University of St Andrews, St Andrews, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Tom Owen-Hughes

    Centre for Gene Regulation and Expression, University of Dundee, Dundee, United Kingdom
    For correspondence
    t.a.owenhughes@dundee.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0618-8185

Funding

Wellcome (95062)

  • Ramasubramanian Sundaramoorthy
  • Amanda L Hughes
  • Hassane El-Mkami
  • David G Norman
  • Tom Owen-Hughes

European Molecular Biology Organization (ALTF 380-2015)

  • Amanda L Hughes

Wellcome (94090)

  • Ramasubramanian Sundaramoorthy
  • Amanda L Hughes
  • Hassane El-Mkami
  • David G Norman
  • Tom Owen-Hughes

Wellcome (99149)

  • Ramasubramanian Sundaramoorthy
  • Amanda L Hughes
  • Hassane El-Mkami
  • David G Norman
  • Tom Owen-Hughes

Wellcome (97945)

  • Ramasubramanian Sundaramoorthy
  • Amanda L Hughes
  • Hassane El-Mkami
  • David G Norman
  • Tom Owen-Hughes

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

Copyright

© 2018, Sundaramoorthy 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

  • 5,401
    views
  • 943
    downloads
  • 75
    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. Ramasubramanian Sundaramoorthy
  2. Amanda L Hughes
  3. Hassane El-Mkami
  4. David G Norman
  5. Helder Ferreira
  6. Tom Owen-Hughes
(2018)
Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome
eLife 7:e35720.
https://doi.org/10.7554/eLife.35720

Share this article

https://doi.org/10.7554/eLife.35720

Further reading

    1. Chromosomes and Gene Expression
    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
    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.