1. Chromosomes and Gene Expression
  2. Structural Biology and Molecular Biophysics
Download icon

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
Research Article
  • Cited 32
  • Views 3,983
  • Annotations
Cite this article as: eLife 2018;7:e35720 doi: 10.7554/eLife.35720

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.

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.

Reviewing Editor

  1. Geeta J Narlikar, University of California, San Francisco, United States

Publication history

  1. Received: February 6, 2018
  2. Accepted: July 24, 2018
  3. Accepted Manuscript published: August 6, 2018 (version 1)
  4. Version of Record published: August 31, 2018 (version 2)

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

  • 3,983
    Page views
  • 827
    Downloads
  • 32
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

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)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Chromosomes and Gene Expression
    Siheng Xiang, Douglas Koshland
    Research Article Updated

    Cohesin helps mediate sister chromatid cohesion, chromosome condensation, DNA repair, and transcription regulation. We exploited proximity-dependent labeling to define the in vivo interactions of cohesin domains with DNA or with other cohesin domains that lie within the same or in different cohesin complexes. Our results suggest that both cohesin's head and hinge domains are proximal to DNA, and cohesin structure is dynamic with differential folding of its coiled coil regions to generate butterfly confirmations. This method also reveals that cohesins form ordered clusters on and off DNA. The levels of cohesin clusters and their distribution on chromosomes are cell cycle-regulated. Cohesin clustering is likely necessary for cohesion maintenance because clustering and maintenance uniquely require the same subset of cohesin domains and the auxiliary cohesin factor Pds5p. These conclusions provide important new mechanistic and biological insights into the architecture of the cohesin complex, cohesin–cohesin interactions, and cohesin's tethering and loop-extruding activities.

    1. Chromosomes and Gene Expression
    2. Medicine
    Karthik Amudhala Hemanthakumar et al.
    Research Article

    Aging, obesity, hypertension and physical inactivity are major risk factors for endothelial dysfunction and cardiovascular disease (CVD). We applied fluorescence-activated cell sorting (FACS), RNA sequencing and bioinformatic methods to investigate the common effects of CVD risk factors in mouse cardiac endothelial cells (ECs). Aging, obesity and pressure overload all upregulated pathways related to TGF-b signaling and mesenchymal gene expression, inflammation, vascular permeability, oxidative stress, collagen synthesis and cellular senescence, whereas exercise training attenuated most of the same pathways. We identified collagen chaperone Serpinh1 (also called as Hsp47) to be significantly increased by aging and obesity and repressed by exercise training. Mechanistic studies demonstrated that increased SERPINH1 in human ECs induced mesenchymal properties, while its silencing inhibited collagen deposition. Our data demonstrate that CVD risk factors significantly remodel the transcriptomic landscape of cardiac ECs inducing inflammatory, senescence and mesenchymal features. SERPINH1 was identified as a potential therapeutic target in ECs.