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.
Sequencing data have been deposited in GEO under accession code GSE129928.
H3K9me2 protects lifespan against the transgenerational burden of germline transcription in C. elegansNCBI Gene Expression Omnibus, GSE129928.
- 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
© 2019, Lee et al.
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