• Media type: E-Article
  • Title: Repressive H3K9me2 protects lifespan against the transgenerational burden of COMPASS activity in C. elegans
  • Contributor: Lee, Teresa Wei-sy; David, Heidi Shira; Engstrom, Amanda Kathryn; Carpenter, Brandon Scott; Katz, David John
  • imprint: eLife Sciences Publications, Ltd, 2019
  • Published in: eLife
  • Language: English
  • DOI: 10.7554/elife.48498
  • ISSN: 2050-084X
  • Origination:
  • Footnote:
  • Description: <jats:p>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.</jats:p>
  • Access State: Open Access