Transgenerational inheritance of altered H3K27me3 in wild-type Caenorhabditis elegans

Abstract Epigenetic inheritance provides mutation-free mechanisms for phenotypic adaptation, including modifications to DNA or DNA-associated proteins that create patterns of heritable gene regulation. However, the limits and regulation of this inheritance remain incompletely understood. Here, we developed a C. elegans system to study the transgenerational epigenetic inheritance of H3K27me3, a conserved histone posttranslational modification associated with gene repression. We find that transiently induced alterations of the genome-wide H3K27me3 landscape and the associated fertility defects persist for many generations in genetically wildtype descendants under selective pressure. We uncover that the inheritance of the altered H3K27me3 landscape involves an initiation phase that relies on SET-32/H3K23me3 and a maintenance phase that requires MES-4/H3K36me3. Our results indicate that epigenetic inheritance can act as a mutation-independent, heritable mechanism of adaptation.