Gene Environment Interactions - Implications for Epigenesis. Yoav Soen. Biological chemistry, Weizmann Institute of Science, Rehovot, Israel.

   Studies of gene regulation often focus on defined genetic programs, ignoring the ability of the environment to promote multiple genotype-to-phenotype transformations and the potential of epigenetics to influence multiple generations of non-exposed offspring. We investigate epigenetic implications of gene-environment interactions using a synthetic drug/anti-drug system which allows us to confront the development of the fly, D. melanogaster, with artificial distributions of toxic stress that are not expected to occur during fly development. Survival of the flies in this system depends of their ability to modify their development. We found that under a wide range of toxic scenarios, the challenge modifies the otherwise robust patterns of development, resulting in changes in gene expression as well as in the rate of larval development and adult morphology (in some of the cases). We show that part of this response is enabled by suppression of Polycomb group genes (PcG), which leads to de-repression of developmental regulators and their expression in new domains, hence the change in developmental patterns. Remarkably, some of the developmental alterations were non-genetically inherited by subsequent generations of unchallenged offspring suggesting that the challenge also modifies the germline of the flies. This was indeed confirmed by analysis of maternal RNA in eggs of challenged versus unchallenged flies. These results reveal a process of epigenesis by which stressful, non-familiar environment suppresses the Polycomb system and induces developmental modifications that persist across generations through non-Mendelian mechanisms.