title: Transcription factors SF1 and cJUN cooperate to activate the Fdx1 promoter in MA-10 Leydig cells.
abstract: The Ferredoxin 1 (FDX1) protein supports steroid biosynthesis in steroidogenic cells through electron transfer to the rate-limiting steroidogenic enzyme, CYP11A1. The latter catalyzes the conversion of cholesterol to pregnenolone through side chain cleavage inside the mitochondria. Thus far, only several transcription factors have been implicated in the regulation of mouse Fdx1 promoter activity in Leydig cells. These include the nuclear receptor SF1 and SP1. Since two conserved regulatory elements for AP1 transcription factors have been located at -764 and -617bp of the Fdx1 promoter, we hypothesized that cJUN may cooperate with other partners to regulate Fdx1 in Leydig cells. Indeed, we report that SF1 and cJUN interact and cooperate to activate the Fdx1 promoter in MA-10 and TM3 Leydig cells. Furthermore, we found that such activation requires different regulatory elements located between -124 and -306bp of the Fdx1 promoter and involves recruitment of SF1 to this region. Using RNA interference, the importance of SF1 in transcriptional regulation of Fdx1 was confirmed, whereas cJUN was dispensable even though it cooperated with SF1 to upregulate Fdx1 expression in MA-10 cells. Thus, our data provides new insights in the molecular mechanisms that control mouse Fdx1 transcription, possibly leading to regulation of CYP11A1 enzyme activation, in Leydig cells.
authors.affiliation: Biology Department, Université de Moncton, Moncton, New-Brunswick, E1A 3E9, Canada.
authors.forename: Pauline
authors.initials: P
authors.lastname: Roumaud
authors.affiliation: Biology Department, Université de Moncton, Moncton, New-Brunswick, E1A 3E9, Canada.
authors.forename: Arlette
authors.initials: A
authors.lastname: Rwigemera
authors.affiliation: Biology Department, Université de Moncton, Moncton, New-Brunswick, E1A 3E9, Canada,. Electronic address: Luc.Martin@umoncton.ca.
authors.forename: Luc J
authors.initials: LJ
authors.lastname: Martin
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D000242:Cyclic AMP / Q000378:metabolism; D005288:Ferredoxins / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D047468:Immunoprecipitation; D007985:Leydig Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D000072260:RNA Splicing Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D020218:Response Elements; D015290:Second Messenger Systems
chemical_list: D005288:Ferredoxins; D016755:Proto-Oncogene Proteins c-jun; D000072260:RNA Splicing Factors; D011993:Recombinant Fusion Proteins; C491514:Sf1 protein, mouse; D000242:Cyclic AMP
keywords: AP1; Fdx1; Leydig cells; NR5A1; SF1; Steroidogenesis; cJUN