title: Heterodimer of two bHLH-PAS proteins mediates juvenile hormone-induced gene expression.
abstract: Juvenile hormone (JH) plays crucial roles in many aspects of insect life. The Methoprene-tolerant (Met) gene product, a member of the bHLH-PAS family of transcriptional regulators, has been demonstrated to be a key component of the JH signaling pathway. However, the molecular function of Met in JH-induced signal transduction and gene regulation remains to be fully elucidated. Here we show that a transcriptional coactivator of the ecdysteroid receptor complex, FISC, acts as a functional partner of Met in mediating JH-induced gene expression. Met and FISC appear to use their PAS domains to form a dimer only in the presence of JH or JH analogs. In newly emerged adult female mosquitoes, expression of some JH responsive genes is considerably dampened when Met or FISC is depleted by RNAi. Met and FISC are found to be associated with the promoter of the early trypsin gene (AaET) when transcription of this gene is activated by JH. A juvenile hormone response element (JHRE) has been identified in the AaET upstream regulatory region and is bound in vitro by the Met-FISC complex present in the nuclear protein extracts of previtellogenic adult female mosquitoes. In addition, the Drosophila homologs of Met and FISC can also use this mosquito JHRE to activate gene transcription in response to JH in a cell transfection assay. Together, the evidence indicates that Met and FISC form a functional complex on the JHRE in the presence of JH and directly activate transcription of JH target genes.
authors.affiliation: Department of Biochemistry, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.forename: Edward A
authors.initials: EA
authors.lastname: Mead
authors.forename: Jinsong
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D019281:Dimerization; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D005786:Gene Expression Regulation; D015723:Gene Library; D020868:Gene Silencing; D007605:Juvenile Hormones / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020218:Response Elements; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029721:Drosophila Proteins; D007605:Juvenile Hormones; D014157:Transcription Factors; C111234:MET protein, Drosophila