Reduction in maternal Polycomb levels contributes to transgenerational inheritance of a response to toxic stress in flies

Key points Previous work on epigenetic transgenerational phenomena focused on chromatin modifications or small RNAs as potential carriers of non-genetic transgenerational influence. We describe a hitherto non-appreciated mode of trans-generational influence by which physiological stress in one generation can impact multiple generations of non-exposed offspring. This mode of transfer involves persistent changes in the composition of maternal RNA in the early offspring embryos. In particular we show that reduction in maternal Polycomb gene levels have a functional contribution to trans-generational inheritance of induced gene expression. Our findings extend the mechanistic repertoire of epigenetic inheritance by providing evidence connecting changes in maternal RNA with trans-generational inheritance of induced phenotypes. Abstract Transgenerational persistence of parental responses to environmental stimuli has been reported in various organisms, but the underlying mechanisms remain underexplored. In one of these reported examples, we have shown that exposure of fly larvae to G418 antibiotic leads to non-Mendelian inheritance of ectopic induction of certain developmental genes. Here we investigate if this inheritance involves changes in mRNA composition within the early, maternal-stage offspring embryos of exposed flies. Exposure to G418 in F1 modified the maternal RNA levels of many genes in their early (F2) embryos. This includes reduction of maternal Polycomb group genes which persisted in the following generation of embryos (F3). To investigate the functional meaning of this reduction, we compared genetically normal embryos of Polycomb mutant females to normal embryos of normal females. Analysis with two different alleles of Polycomb, Pc1 and Pc3, revealed that maternal reduction in Polycomb gene dosage has a positive influence on the inheritance of induced expression. Together, this shows that exposure to G418 stress reduces the maternal levels of Polycomb in the offspring embryos and this reduction contributes to the inheritance of induced expression.