The Transcription Factors Steroidogenic Factor-1 and SOX9 Regulate Expression of Vanin-1 during Mouse Testis Development

Abstract

We previously showed, using differential expression screening and in situ hybridization that Vanin-1, which encodes a glycosylphosphatidylinositol-linked membrane-associated pantetheinase, is expressed in a sex-specific manner during fetal gonad development in mice (Bowles, J., Bullejos, M., and Koopman, P. (2000) Genesis 27, 124-135). In the present study we investigate in detail the expression and regulation of Vanin-1 in the fetal testis. Vanin-1 is co-expressed with the transcription factors steroidogenic factor-1 (SF-1) and SOX9 in Sertoli cells and, at a lower level, with SF-1 in Leydig cells in developing testes. SF-1 is able to activate the transcription of the Vanin-1 promoter in in vitro reporter assays, and this activation is further augmented by SOX9. We found that SF-1 is able to bind to two sites in the Vanin-1 promoter, whereas SOX9 can bind to a single interposed site defined by DNA footprinting. Mutation of the SF-1 or SOX9 sites disrupts the binding of these factors and activation of transcription. The expression of Vanin-1 was abolished in Leydig cells of a mouse mutant lacking SF-1 in that cell type. Our findings account for the sex- and cell-type-specific expression of Vanin-1 in the developing mouse gonad in vivo, which we suggest is required to provide an appropriate environment for male germ cell development.