1. Microbiology and Infectious Disease
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Modifications at K31 on the lateral surface of histone H4 contribute to genome structure and expression in apicomplexan parasites

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Cite this article as: eLife 2017;6:e29391 doi: 10.7554/eLife.29391

Abstract

An unusual genome architecture characterizes the two related human parasitic pathogens Plasmodium falciparum and Toxoplasma gondii. A major fraction of the bulk parasite genome is packaged as transcriptionally permissive euchromatin with few loci embedded in silenced heterochromatin. Primary chromatin shapers include histone modifications at the nucleosome lateral surface close to the DNA but their mode of action remains unclear. We now identify versatile modifications at Lys31 within the globular domain of histone H4 that crucially determine genome organization and expression in Apicomplexa parasites. H4K31 acetylation at the promoter correlates with, and perhaps directly regulates, gene expression in both parasites. In contrast, monomethylated H4K31 is enriched in the core body of T. gondii active genes but inversely correlates with transcription while being unexpectedly enriched at transcriptionally inactive pericentromeric heterochromatin in P. falciparum, a region devoid of the characteristic H3K9me3 histone mark and its downstream effector HP1.

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Author details

  1. Fabien Sindikubwabo

    Institute for Advanced Biosciences - U1209, INSERM, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Shuai Ding

    Unité de Biologie des Interactions Hôte-Parasite, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Tahir Hussain

    Institute for Advanced Biosciences - U1209, INSERM, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Philippe Ortet

    UMR 7265, CEA, Cadarache, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Mohamed Barakat

    UMR 7265, CEA, Cadarache, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Sebastian Baumgarten

    Unité de Biologie des Interactions Hôte-Parasite, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Dominique Cannella

    Institute for Advanced Biosciences - U1209, INSERM, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Andrés Palencia

    Institute for Advanced Biosciences - U1209, INSERM, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1805-319X
  9. Alexandre Bougdour

    Institute for Advanced Biosciences - U1209, INSERM, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  10. Lucid Belmudes

    BIG-BGE, CEA, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  11. Yohann Couté

    BIG-BGE, CEA, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3896-6196
  12. Isabelle Tardieux

    Institute for Advanced Biosciences - U1209, CNRS, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  13. Cyrille Y Botté

    Institute for Advanced Biosciences - U1209, CNRS, Grenoble, France
    Competing interests
    The authors declare that no competing interests exist.
  14. Artur Scherf

    Unité de Biologie des Interactions Hôte-Parasite, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  15. Mohamed-ali Hakimi

    Institute for Advanced Biosciences - U1209, INSERM, Grenoble, France
    For correspondence
    mohamed-ali.hakimi@inserm.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2547-8233

Funding

European Commission (ERC Consolidator Grant No. 614880)

  • Fabien Sindikubwabo
  • Dominique Cannella
  • Mohamed-ali Hakimi

European Commission (ERC AdG No. 670301)

  • Artur Scherf

Agence Nationale de la Recherche (ANR-10-INBS-08-01)

  • Lucid Belmudes
  • Yohann Couté

Agence Nationale de la Recherche (LABEX PARAFRAP ANR-11-LABX-0024)

  • Fabien Sindikubwabo
  • Shuai Ding
  • Tahir Hussain
  • Dominique Cannella
  • Andrés Palencia
  • Alexandre Bougdour
  • Cyrille Y Botté
  • Artur Scherf
  • Mohamed-ali Hakimi

Agence Nationale de la Recherche (ANR-12-BSV3-0009-01)

  • Dominique Cannella
  • Andrés Palencia
  • Alexandre Bougdour
  • Mohamed-ali Hakimi

Agence Nationale de la Recherche (ANR-12-PDOC-0028)

  • Cyrille Y Botté

CNRS-INSERM-Fondation FINOVI (Atip-Avenir Program Project Apicolipid)

  • Cyrille Y Botté

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

Reviewing Editor

  1. Daniel Zilberman, University of California, Berkeley, United States

Publication history

  1. Received: June 7, 2017
  2. Accepted: November 2, 2017
  3. Accepted Manuscript published: November 4, 2017 (version 1)
  4. Accepted Manuscript updated: November 7, 2017 (version 2)
  5. Version of Record published: November 14, 2017 (version 3)

Copyright

© 2017, Sindikubwabo 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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