title: The Drosophila FTZ-F1 nuclear receptor mediates juvenile hormone activation of E75A gene expression through an intracellular pathway.
abstract: Juvenile hormone (JH) regulates a wide variety of biological activities in holometabolous insects, ranging from vitellogenesis and caste determination in adults to the timing of metamorphosis in larvae. The mechanism of JH signaling in such a diverse array of processes remains either unknown or contentious. We previously found that the nuclear receptor gene E75A is activated in S2 cells as a primary response to JH. Here, by expressing an intracellular form of JH esterase, we demonstrate that JH must enter the cell in order to activate E75A. To find intracellular receptors involved in the JH response, we performed an RNAi screen against nuclear receptor genes expressed in this cell line and identified the orphan receptor FTZ-F1. Removal of FTZ-F1 prevents JH activation of E75A, whereas overexpression enhances activation, implicating FTZ-F1 as a critical component of the JH response. FTZ-F1 is bound in vivo to multiple enhancers upstream of E75A, suggesting that it participates in direct JH-mediated gene activation. To better define the role of FTZ-F1 in JH signaling, we investigated interactions with candidate JH receptors and found that the bHLH-PAS proteins MET and GCE both interact with FTZ-F1 and can activate transcription through the FTZ-F1 response element. Removal of endogenous GCE, but not MET, prevents JH activation of E75A. We propose that FTZ-F1 functions as a competence factor by loading JH signaling components to the promoter, thus facilitating the direct regulation of E75A gene expression by JH.
authors.affiliation: Department of Biology, Fordham University, Bronx, New York 10458, USA. dubrovsky@fordham.edu
authors.forename: Edward B
authors.initials: EB
authors.lastname: Dubrovsky
authors.forename: Veronica A
authors.initials: VA
authors.lastname: Dubrovskaya
authors.forename: Travis
authors.initials: T
authors.lastname: Bernardo
authors.forename: Valerie
authors.initials: V
authors.lastname: Otte
authors.forename: Robert
authors.initials: R
authors.lastname: DiFilippo
authors.forename: Heather
authors.initials: H
authors.lastname: Bryan
mesh_terms: D000818:Animals; D001483:Base Sequence; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D007605:Juvenile Hormones / Q000494:pharmacology*; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D020218:Response Elements / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D024363:Transcription Initiation Site; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D007605:Juvenile Hormones; D014157:Transcription Factors; C499712:nuclear hormone receptor FTZ-F1, Drosophila; C061375:Eip75B protein, Drosophila; D002265:Carboxylic Ester Hydrolases; C038003:juvenile hormone esterase