Stable Polycomb-dependent transgenerational inheritance of chromatin states in Drosophila

Transgenerational epigenetic inheritance entails transmission of epigenetically determined phenotypic traits through multiple generations. However, very little is known on the principles and the mechanisms governing this type of inheritance. Here, we established stable and isogenic Drosophila epilines by transiently enhancing long-range chromatin interactions. Such epilines display two opposing chromatin states, which depend on differential levels of the H3K27me3 histone mark. Once established, both the active and the repressed epialleles can dominantly be transmitted to naïve flies and can induce paramutation. Importantly, both epilines can be reset to an intermediate naïve state by disrupting chromatin interactions. Finally, we show that the environment can modulate the expressivity of the epialleles and we extend our paradigm to naturally occurring genetic makeups. Our work sheds light on how nuclear organization contributes to epigenetically heritable phenotypic variability and therefore to evolution. Overall design: genomic DNA sequencing and RNA sequencing of Drosophila melanogaster epilines