A STEROID-TRIGGERED SWITCH IN E74 TRANSCRIPTION FACTOR ISOFORMS REGULATES THE TIMING OF SECONDARY-RESPONSE GENE-EXPRESSION

The steroid hormone 20-hydroxyecdysone (referred to here as ecdysone) directs Drosophila metamorphosis by activating a series of genetic reg ulatory hierarchies, ETS domain transcription factors encoded by the e cdysone-inducible E74 early gene, E74A and E74B, act at the top of the se hierarchies to coordinate the induction of target genes, We have ec topically expressed these E74 isoforms to understand their regulatory functions during the onset of metamorphosis, We shaw that E74 can regu late its own transcription, most likely through binding sites within i ts gene, Ectopic expression of E74B can partially repress the E78B and DHR3 orphan receptor genes, suggesting a role for E74 in the appropri ate timing of early-late gene expression, Furthermore, E74A is both ne cessary and sufficient for E78B induction, implicating E74A as a key r egulator of E78B expression. We also show, consistent with our studies of E74 loss-of-function mutations, that E74B is a patent repressor of late gene transcription and E74A is sufficient to prematurely induce the L71-1 late gene, However, ectopic expression of both Broad-Complex and E74A activators in an E74B mutant background is not sufficient to prematurely induce all late genes, indicating that other factors cont ribute to this regulatory circuit, ?these observations demonstrate tha t the steroid-triggered switch in E74 transcription factor isoforms pl ays a central role in the proper timing of secondary-response gene exp ression.