The Polycomb Repressive Complex 2.1 Links the Food Environment to a Persistent Neural State

Interactions between genes and environment sculpt the responses of cells to environmental stimuli. In neuronal cells this process can lead to long term changes in the behavioral repertoire of animals, which in turn impacts disease risk. Here we show that the Polycomb Repressive Complex 2.1 (PRC2.1) modulates the physiology of sweet gustatory neurons and the taste behavior of D. melanogaster fruit flies in response to the food environment. A high sugar diet caused a redistribution of PRC2.1 chromatin occupancy resulting in the repression of a transcriptional network required for the responsiveness of the gustatory neurons to sweet stimuli. These changes led to lower sweet sensation, which in turn promoted obesity. Nearly half of the transcriptional changes mediated by PRC2.1 on a sugar diet persisted when animals were moved back to a control diet, causing a permanent decrease in sweet taste that was dependent on the constitutive activity of PRC2.1. Thus, our results point to a novel mechanism involved in modulating neural plasticity, behavior, and disease in response to the food environment.