A steroid receptor coactivator acts as the DNA-binding partner of the methoprene-tolerant protein in regulating juvenile hormone response genes.

Methoprene-tolerant (Met) protein is a juvenile hormone (JH) receptor in insects. JH-bound Met forms a complex with the bFtz-F1-interacting steroid receptor coactivator (FISC) and together they regulate JH response genes in mosquitoes. Both proteins contain basic helix–loop–helix (bHLH) and PAS motifs. Here we demonstrated that FISC is the obligatory partner of Met for binding to JH-response elements (JHREs). Met or FISC alone could not bind a previously characterized JHRE, while formation of the Met–FISC complex was necessary and sufficient to bind to the JHRE. This binding required participation of the DNA-binding domains of both Met and FISC. The optimal DNA sequence recognized by Met and FISC contained a core consensus sequence GCACGTG. While formation of the Met–FISC complex in mosquito cells was induced by JH, heterodimerization and DNA binding of bacterially expressed Met and FISC were JH-independent, implying that additional mosquito proteins were required to modulate formation of the receptor complex.