If flies eat a high sugar diet (HSD) long enough, the sensory response to sweet taste is dulled, even after returning to a normal diet. @anoumid in @Hardkandy000's lab shows this is due to a persistent alteration in chromatin state. https://doi.org/10.1126/sciadv.abc8492

A screen for factors that regulate the desensitization to sweetness on a HSD identified components of polycomb repressive complex 2.1 (PRC2.1). Inhibition or mutation of PRC2.1 prevents desensitization.

The authors then use DamID TaDa (stupid name, but VERY cool technique-I'd-never-heard-of) to identify chromatin occupancy sites of PRC2.1 component Pcl on control and HSD. Pcl occupancy is redistributed on HSD!

The authors also use TRAP to find differential gene expression on control and HSD in WT and Pcl-mutant flies. They identify 5 key trx regulators that have differential Pcl binding and substantial changes in gene expression by diet.

KD of the activators or OE of the repressor blunted sweet taste sensitivity. There are at least 658 (!) target genes potentially regulated by these 5 trx factors - including each other! Turns out they form a regulatory hub.

Remember how flies keep being desensitized to sweetness after returning to control diet from HSD? PRC2.1 is required for this "taste memory." Inhibiting PRC2.1 allows flies to return to normal taste sensitivity when returned to control diet.

The activation of a developmental transcriptional network in response to environment to regulate neural plasticity suggests that while terminally differentiated neurons maintain neural identity, they can repurpose devo programs to modulate (and remember prior) cell states.

After reading this, I wondered if this reengagement of devo programs occurs in other sensory/metabolic neurons, and how coordination across senses in complex environments could create even wider, and maybe more persistent, reprogramming of neural states