title: StarD7 gene expression in trophoblast cells: contribution of SF-1 and Wnt-beta-catenin signaling.
abstract: Steroidogenic acute regulatory protein-related lipid transfer domain containing 7 (StarD7) is a poorly characterized member of the steroidogenic acute regulatory protein-related lipid transfer proteins, up-regulated in JEG-3 cells, involved in intracellular transport and metabolism of lipids. Previous studies dealing with the mechanisms underlying the human StarD7 gene expression led us to define the cis-acting regulatory sequences in the StarD7 promoter using as a model JEG-3 cells. These include a functional T cell-specific transcription factor 4 (TCF4) site involved in Wnt-β-catenin signaling. To understand these mechanisms in more depth, we examined the steroidogenic factor 1 (SF-1) contribution to StarD7 expression. Cotransfection experiments in JEG-3 cells point out that the StarD7 promoter is activated by SF-1, and this effect is increased by forskolin. EMSA using JEG-3 nuclear proteins demonstrated that SF-1 binds to the StarD7 promoter. Additionally, chromatin immunoprecipitation analysis indicated that SF-1 and β-catenin are bound in vivo to the StarD7 promoter. Reporter gene assays in combination with mutations in the SF-1 and TCF4 binding sites revealed that the StarD7 promoter is synergistically activated by SF-1 and β-catenin and that the TCF4 binding site (-614/-608) plays an important role in this activation. SF-1 amino acid mutations involved in the physical interaction with β-catenin abolished this activation; thus demonstrating that the contact between the two proteins is necessary for an efficient StarD7 transcriptional induction. Finally, these data suggest that β-catenin could function as a bridge between SF-1 and TCF4 forming a ternary complex, which would stimulate StarD7 expression. The SF-1 and β-catenin pathway convergence on StarD7 expression may have important implications in the phospholipid uptake and transport, contributing to the normal trophoblast development.
authors.affiliation: Universidad Nacional de Córdoba-Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica-Centro de Investigaciones en Bioquímica Clínica e Inmunología, X5000HUA Córdoba, Argentina.
authors.forename: Viviana
authors.initials: V
authors.lastname: Rena
authors.forename: Jésica
authors.initials: J
authors.lastname: Flores-Martín
authors.forename: Sofía
authors.initials: S
authors.lastname: Angeletti
authors.forename: Graciela M
authors.initials: GM
authors.lastname: Panzetta-Dutari
authors.forename: Susana
authors.initials: S
authors.lastname: Genti-Raimondi
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D000242:Cyclic AMP / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008024:Ligands; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D054339:Steroidogenic Factor 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D008024:Ligands; C483475:STARD7 protein, human; D054339:Steroidogenic Factor 1; D051153:Wnt Proteins; D051176:beta Catenin; D000242:Cyclic AMP