Transgenerational maintenance of H3K27me3 heterochromatin is balanced by chromodomain proteins in Caenorhabditis elegans

The ability to replicate and pass information to descendants is a fundamental requirement for life. In addition to the DNA-based genetic information, modifications of the DNA or DNA-associated proteins can create patterns of heritable gene regulation. Such epigenetic inheritance allows for adaptation without mutation, but its limits and regulation are 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 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 is regulated by two chromodomain proteins with antagonizing functions, and provide mechanistic insight into how this molecular memory is initiated and maintained. Our results demonstrate that epigenetic inheritance can act as a mutation-independent, heritable mechanism of adaptation.