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Norway

PMID:31815663  

Repressive H3K9me2 protects lifespan against the transgenerational burden of COMPASS activity in C. elegans.

Teresa Wei-Sy Lee | Heidi Shira David | Amanda Kathryn Engstrom | Brandon Scott Carpenter | David John Katz
eLife | 2019

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.

Pubmed ID: 31815663

Associated grants

  • Agency: NIH HHS, United States
    Id: K12GM00680-15
  • Agency: National Science Foundation, International
    Id: IOS1354998
  • Agency: NIGMS NIH HHS, United States
    Id: F32 GM126734
  • Agency: NIH HHS, United States
    Id: F31 NS098663-02
  • Agency: NINDS NIH HHS, United States
    Id: F31 NS098663
  • Agency: NIGMS NIH HHS, United States
    Id: K12 GM000680
  • Agency: NIH HHS, United States
    Id: F31 NS098663-01A1

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