The transcription factors steroidogenic factor-1 and SOX9 regulate expression of Vanin-1 during mouse testis development.
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.
Wilson
Megan J
MJ
Institute for Molecular Bioscience, the University of Queensland, Brisbane 4072, Queensland, Australia.
Jeyasuria
Pancharatnam
P
Parker
Keith L
KL
Koopman
Peter
P
D000581:Amidohydrolases; D000818:Animals; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D058851:GPI-Linked Proteins; D017930:Genes, Reporter / Q000235:genetics; D006609:High Mobility Group Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D009154:Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D055758:SOX9 Transcription Factor; D055757:SOXE Transcription Factors; D054339:Steroidogenic Factor 1; D013737:Testis / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics
D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D058851:GPI-Linked Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D055758:SOX9 Transcription Factor; D055757:SOXE Transcription Factors; C498639:Sox8 protein, mouse; C527933:Sox9 protein, mouse; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; D004247:DNA; D003850:Deoxyribonuclease I; D000581:Amidohydrolases; C022314:pantetheinase