A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis

  1. Nicolas Altemose  Is a corresponding author
  2. Nudrat Noor
  3. Emmanuelle Bitoun
  4. Afidalina Tumian
  5. Michael Imbeault
  6. J Ross Chapman
  7. A Radu Aricescu
  8. Simon R Myers  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. École Polytechnique Fédérale de Lausanne, Switzerland

Abstract

PRDM9 binding localizes almost all meiotic recombination sites in humans and mice. However, most PRDM9-bound loci do not become recombination hotspots. To explore factors that affect binding and subsequent recombination outcomes, we mapped human PRDM9 binding sites in a transfected human cell line and measured PRDM9-induced histone modifications. These data reveal varied DNA-binding modalities of PRDM9. We also find that human PRDM9 frequently binds promoters, despite their low recombination rates, and it can activate expression of a small number of genes including CTCFL and VCX. Furthermore, we identify specific sequence motifs that predict consistent, localized meiotic recombination suppression around a subset of PRDM9 binding sites. These motifs strongly associate with KRAB-ZNF protein binding, TRIM28 recruitment, and specific histone modifications. Finally, we demonstrate that, in addition to binding DNA, PRDM9's zinc fingers also mediate its multimerization, and we show that a pair of highly diverged alleles preferentially form homo-multimers.

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Author details

  1. Nicolas Altemose

    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
    For correspondence
    altemose@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7231-6026
  2. Nudrat Noor

    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Emmanuelle Bitoun

    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Afidalina Tumian

    Department of Statistics, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Michael Imbeault

    Global Health Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0073-0922
  6. J Ross Chapman

    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6477-4254
  7. A Radu Aricescu

    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3783-1388
  8. Simon R Myers

    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
    For correspondence
    myers@stats.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Funding

Wellcome (Investigator Award 098387/Z/12/Z)

  • Simon R Myers

Cancer Research UK (Career Development Fellowship C52690/A19270)

  • J Ross Chapman

Howard Hughes Medical Institute (Gilliam Fellowship for Advanced Study)

  • Nicolas Altemose

Medical Research Council (Grant MR/L009609/1)

  • A Radu Aricescu

Foreign and Commonwealth Office (Marshall Scholarship)

  • Nicolas Altemose

Wellcome (Core Award 090532/Z/09/Z)

  • Nicolas Altemose
  • Nudrat Noor
  • Emmanuelle Bitoun
  • J Ross Chapman
  • A Radu Aricescu
  • Simon R Myers

Wellcome (DPhil Studentship 086817/Z/08/Z)

  • Nudrat Noor

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

Reviewing Editor

  1. Molly Przeworski, Columbia University, United States

Version history

  1. Received: May 5, 2017
  2. Accepted: October 24, 2017
  3. Accepted Manuscript published: October 26, 2017 (version 1)
  4. Version of Record published: November 28, 2017 (version 2)

Copyright

© 2017, Altemose 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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  1. Nicolas Altemose
  2. Nudrat Noor
  3. Emmanuelle Bitoun
  4. Afidalina Tumian
  5. Michael Imbeault
  6. J Ross Chapman
  7. A Radu Aricescu
  8. Simon R Myers
(2017)
A map of human PRDM9 binding provides evidence for novel behaviors of PRDM9 and other zinc-finger proteins in meiosis
eLife 6:e28383.
https://doi.org/10.7554/eLife.28383

Share this article

https://doi.org/10.7554/eLife.28383

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