The competence factor beta Ftz-F1 potentiates ecdysone receptor activity via recruiting a p160/SRC coactivator

Hormones provide generalized signals that are interpreted in a specific spatial and temporal manner by a developing or reproducing multicellular organism. The ability to respond to hormones is determined by the competence of a cell or a tissue. The betaFtz-F1 orphan nuclear receptor acts as a competence factor for the steroid hormone 20-hydroxyecdysone (20E) in Drosophila melanogaster metamorphosis and mosquito reproduction. The molecular nature of the betaFtz-F1 action remains unclear. We report that the protein-protein interaction between betaFtz-F1 and a p160/SRC coactivator of the ecdysone receptor, FISC, is crucial for the stage-specific expression of the 20E effector genes during mosquito reproduction. This interaction dramatically increases recruitment of FISC to the functional ecdysone receptor in a 20E-dependent manner. The presence of betaFtz-F1 facilitates loading of FISC and the ecdysone receptor on the target promoters, leading to enhanced local histone H4 acetylation and robust activation of the target genes. Thus, our results reveal the molecular basis of competence for the stage-specific 20E response.