HP1c regulates development and gut homeostasis by suppressing Notch signaling through Su(H)

Abstract

Notch signaling and epigenetic factors are known to play critical roles in regulating tissue homeostasis in most multicellular organ- isms, but how Notch signaling coordinates with epigenetic modu- lators to control differentiation remains poorly understood. Here, we identify heterochromatin protein 1c (HP1c) as an essential epigenetic regulator of gut homeostasis in Drosophila. Specifically, we observe that HP1c loss-of-function phenotypes resemble those observed after Notch signaling perturbation and that HP1c inter- acts genetically with components of the Notch pathway. HP1c represses the transcription of Notch target genes by directly inter- acting with Suppressor of Hairless (Su(H)), the key transcription factor of Notch signaling. Moreover, phenotypes caused by deple- tion of HP1cin Drosophila can be rescued by expressing human HP1c, suggesting that HP1c functions similar to HP1cin Droso- phila. Taken together, our findings reveal an essential role of HP1c in normal development and gut homeostasis by suppressing Notch signaling.