Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans.
Bottom Line: Here we show that deficiencies in the H3K4me3 chromatin modifiers ASH-2, WDR-5 or SET-2 in the parental generation extend the lifespan of descendants up until the third generation.The transgenerational inheritance of lifespan extension by members of the ASH-2 complex is dependent on the H3K4me3 demethylase RBR-2, and requires the presence of a functioning germline in the descendants.Transgenerational inheritance of lifespan is specific for the H3K4me3 methylation complex and is associated with epigenetic changes in gene expression.
Affiliation: Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA.Show MeSH
Mentions: The H3K4me3 demethylase RBR-2 is necessary for the lifespan extension caused by deficiencies in members of the ASH-2 complex12. We asked if the transgenerational extension of longevity induced by deficiencies in members of the ASH-2 complex is dependent on RBR-2. The lifespan of genetically wildtype F3 descendents from P0 wdr-5 parents (+/+ from P0 wdr-5 parents) was no longer extended in the presence of rbr-2 RNAi (Fig. 4a, b). Similarly, F3 wildtype descendents from set-2;rbr-2 parents (+/+ from P0 set-2;rbr-2 parents) were no longer long-lived (Supplementary Fig. 1). Together, these data indicate that the transgenerational inheritance of longevity due to deficiencies in H3K4 trimethylation complex members is dependent on the H3K4me3 demethylase RBR-2. The fact that the longevity of wildtype descendents of wdr-5 and set-2 mutants is reverted by deficiencies in rbr-2 also suggests that this extended lifespan is unlikely to result from extraneous mutations in wdr-5 or set-2 strains. rbr-2 mutation or knock-down did not lead to a shortening of lifespan in descendents (Supplementary Fig. 2), indicating that by itself, RBR-2 deficiency does not affect longevity in a transgenerational manner.
Affiliation: Department of Genetics, Stanford University, 300 Pasteur Drive, Stanford, California 94305, USA.