1. Chromosomes and Gene Expression
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Repressive H3K9me2 protects lifespan against the transgenerational burden of COMPASS activity in C. elegans

  1. Teresa W Lee
  2. Heidi Shira David
  3. Amanda Kathryn Engstrom
  4. Brandon Scott Carpenter
  5. David John Katz  Is a corresponding author
  1. Emory University School of Medicine, United States
Research Article
  • Cited 2
  • Views 1,847
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Cite this article as: eLife 2019;8:e48498 doi: 10.7554/eLife.48498

Abstract

In Caenorhabditis elegans, mutations in WDR-5 and other components of the COMPASS H3K4 methyltransferase complex extend lifespan and enable its inheritance. Here we show that wdr-5 mutant longevity is itself a transgenerational trait that corresponds with a global enrichment of the heterochromatin factor H3K9me2 over twenty generations. In addition, we find that the transgenerational aspects of wdr-5 mutant longevity require the H3K9me2 methyltransferase MET-2, and can be recapitulated by removal of the putative H3K9me2 demethylase JHDM-1. Finally, we show that the transgenerational acquisition of longevity in jhdm-1 mutants is associated with accumulating genomic H3K9me2 that is inherited by their long-lived wild-type descendants at a subset of loci. These results suggest that heterochromatin facilitates the transgenerational establishment and inheritance of a complex trait. Based on these results, we propose that transcription-coupled H3K4me via COMPASS limits lifespan by encroaching upon domains of heterochromatin in the genome.

Article and author information

Author details

  1. Teresa W Lee

    Department of Cell Biology, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0149-5389
  2. Heidi Shira David

    Department of Cell Biology, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Amanda Kathryn Engstrom

    Department of Cell Biology, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Brandon Scott Carpenter

    Department of Cell Biology, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. David John Katz

    Department of Cell Biology, Emory University School of Medicine, Atlanta, United States
    For correspondence
    djkatz@emory.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3040-1142

Funding

National Institutes of Health (K12GM00680-15)

  • Teresa W Lee
  • Brandon Scott Carpenter

National Science Foundation (IOS1354998)

  • David John Katz

National Institutes of Health (F31 NS098663-02)

  • Amanda Kathryn Engstrom

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

Reviewing Editor

  1. Matt Kaeberlein, University of Washington, United States

Publication history

  1. Received: May 15, 2019
  2. Accepted: December 6, 2019
  3. Accepted Manuscript published: December 9, 2019 (version 1)
  4. Version of Record published: January 24, 2020 (version 2)

Copyright

© 2019, Lee 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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