Polycomb regulates sleep homeostasis in a specific group of cells in <i>Drosophila</i> brain

Sleep is regulated by the circadian rhythm and homeostasis. Previous studies have shown that epigenetic factors play a crucial role in controlling sleep homeostasis. However, a global view of the epigenetic target genes involved in sleep homeostasis is still lacking. In this study, we have discovered that Polycomb (Pc) regulates sleep in EB1-Gal4 and R69F08-Gal4 co-expressing cells, which are important for controlling sleep homeostasis. Using Targeted DAM-ID (TaDa) and RNAseq, we have identified Pc targets in EB1-Gal4- and R69F08-Gal4-expressing cells and analyzed Pc targets that are crucial for the control of sleep homeostasis. Furthermore, identifying common targets in EB1-Gal4- and R69F08-Gal4-marked cells provides a global view of the cluster-specific target genes of Pc, which potentially play a crucial role in controlling sleep homeostasis. The clustering of these target gene profiles reveals their enrichment distributions. Further experiments demonstrated that Pc stabilized the expression levels of their targets under conditions of sleep deprivation. This study sheds light on the role of Pc in sleep homeostasis control and identifies its target genes in a cell-specific manner. It also lays the foundation for further studies on the mechanisms of epigenetic regulation of sleep homeostasis.