StarD7 gene expression in trophoblast cells: Contribution of SF-1 and Wnt-b-catenin signalling

RENA VIVIANA; FLORES-MARTÍN JÉSICA; ANGELETTI SOFÍA; PANZETTA-DUTARI GRACIELA; GENTI DE RAIMONDI SUSANA

MOLECULAR ENDOCRINOLOGY

ENDOCRINE SOC

Año: 2011 vol. 25 p. 1364 - 1375

0888-8809

StarD7 is a poorly characterized member of the StAR-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 TCF4 site involved in Wnt--catenin signalling. To understand these mechanisms in more depth, we examined the SF-1 contribution to StarD7 expression. Co-transfection 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 -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 -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.