Repressive H3K9me2 protects lifespan against the transgenerational burden of COMPASS activity in C. elegans
- Emory University School of Medicine, United States
- Cited 2
- Views 1,847
- Annotations
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.
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.
Reviewing Editor
- Matt Kaeberlein, University of Washington, United States
Publication history
- Received: May 15, 2019
- Accepted: December 6, 2019
- Accepted Manuscript published: December 9, 2019 (version 1)
- Version of Record published: January 24, 2020 (version 2)
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.
Metrics
-
- 1,847
- Page views
-
- 365
- Downloads
-
- 2
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
Downloads (link to download the article as PDF)
Download citations (links to download the citations from this article in formats compatible with various reference manager tools)
Open citations (links to open the citations from this article in various online reference manager services)
Further reading
-
- Chromosomes and Gene Expression
-
- Chromosomes and Gene Expression
- Computational and Systems Biology
