Cooperative Control of Ecdysone Biosynthesis in Drosophila by Transcription Factors Seance, Ouija Board, and Molting Defective

Ecdysteroids are steroid hormones that control many aspects of development and physiology. During larval development, ecdysone is synthesized in an endocrine organ called the prothoracic gland through a series of ecdysteroidogenic enzymes encoded by the Halloween genes. The expression of the Halloween genes is highly restricted and dynamic, indicating that their spatiotemporal regulation is mediated by their tight transcriptional control. In this study, we report that three zinc finger-associated domain (ZAD)-C2H2 zinc finger transcription factorsSeance (Sean), Ouija board (Ouib), and Molting defective (Mld)cooperatively control ecdysone biosynthesis in the fruit fly Drosophila melanogaster. Sean and Ouib act in cooperation with Mld to positively regulate the transcription of neverland and spookier, respectively, two Halloween genes. Remarkably, loss-of-function mutations in sean, ouib, or mld can be rescued by the expression of neverland, spookier, or both, respectively. These results suggest that the three transcription factors have distinct roles in coordinating the expression of just two genes in Drosophila. Given that neverland and spookier are located in constitutive heterochromatin, Sean, Ouib, and Mld represent the first example of a transcription factor subset that regulates genes located in constitutive heterochromatin.