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.
- Teresa W Lee
- Brandon Scott Carpenter
- David John Katz
- Amanda Kathryn Engstrom
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Matt Kaeberlein, University of Washington, United States
- Received: May 15, 2019
- Accepted: December 6, 2019
- Accepted Manuscript published: December 9, 2019 (version 1)
© 2019, Lee et al.
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