Repressive H3K9me2 protects lifespan against the transgenerational burden of COMPASS activity in C. elegans
- Emory University School of Medicine, United States
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.
Data availability
Sequencing data have been deposited in GEO under accession code GSE129928.
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H3K9me2 protects lifespan against the transgenerational burden of germline transcription in C. elegansNCBI Gene Expression Omnibus, GSE129928.
Article and author information
Author details
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.
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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Repressive H3K9me2 protects lifespan against the transgenerational burden of COMPASS activity in C. elegans
eLife 8:e48498.
https://doi.org/10.7554/eLife.48498
