1. Chromosomes and Gene Expression
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A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress

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Cite this article as: eLife 2017;6:e21666 doi: 10.7554/eLife.21666

Abstract

Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set of C. elegans heterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways. Remarkably, fertility of heterochromatin mutants could be partially restored by inhibiting cep-1/p53, endogenous meiotic double strand breaks, or the expression of MIRAGE1 DNA transposons. Functional redundancy among these factors and pathways underlies the importance of safeguarding the genome through multiple means.

Article and author information

Author details

  1. Alicia N McMurchy

    The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7033-8790
  2. Przemyslaw Stempor

    The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  3. Tessa Gaarenstroom

    Department of Genetics, The Gurdon Institute, University of Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  4. Brian Wysolmerski

    The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  5. Yan Dong

    The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  6. Darya Aussianikava

    The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  7. Alex Appert

    The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  8. Ni Huang

    The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8849-038X
  9. Paulina Kolasinska-Zwierz

    The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  10. Alexandra Sapetschnig

    The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
  11. Eric A Miska

    The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4450-576X
  12. Julie Ahringer

    The Gurdon Institute, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    ja219@cam.ac.uk
    Competing interests
    Julie Ahringer, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7074-4051

Funding

Wellcome (54523)

  • Julie Ahringer

Wellcome (101863)

  • Julie Ahringer

Canadian Institutes of Health Research

  • Alicia N McMurchy

Cancer Research UK (C13474/A18583)

  • Eric A Miska

Human Frontier Science Program

  • Alexandra Sapetschnig

Wellcome (104640/Z/14/Z)

  • Eric A Miska

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

Reviewing Editor

  1. Edith Heard, Institut Curie, France

Publication history

  1. Received: September 20, 2016
  2. Accepted: March 10, 2017
  3. Accepted Manuscript published: March 15, 2017 (version 1)
  4. Version of Record published: April 18, 2017 (version 2)
  5. Version of Record updated: October 5, 2017 (version 3)

Copyright

© 2017, McMurchy 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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