Croft, Jaime et al. (2021) International Worm Meeting "The transgenerational accumulation of repressive H3K9me2 affects health and lifespan in C. elegans"

Lee, Teresa, Croft, Jaime

[International Worm Meeting, 2021]

In Caenorhabditis elegans, mutations in WDR-5 and other components of the COMPASS H3K4 methyltransferase complex extend lifespan and enable its inheritance. Previously, we have shown that wdr-5 mutant longevity is itself a transgenerational trait that corresponds with a global enrichment of the heterochromatin factor H3K9me2 over twenty generations. Additionally, the transgenerational aspects of wdr-5 mutant longevity require the H3K9me2 methyltransferase MET-2 and are recapitulated by removal of the putative H3K9me2 demethylase JHDM-1. In both wdr-5 mutants and jhdm-1 mutants, the transgenerational acquisition of longevity is associated with a generational increase of the repressive modification H3K9me2. These results suggest that repressive chromatin facilitates the transgenerational establishment and inheritance of a complex trait. Intriguingly, we find that although both mutants eventually attain longevity, they do so with different generational dynamics and striking differences in health. Therefore, the genomic accumulation of repressive H3K9me2 may target pathways that will shed light on the complicated relationship between health and lifespan.