SRY protein enhances transcription of Fos-related antigen 1 promoter constructs.

In mammals, testis determination is under the control of the chromosome Y-linked SRY gene. Sry is expressed in the fetal mouse just before development of the testis and shows germ-cell-dependent expression in the adult mouse. SRY protein contains a high-mobility-group (HMG)-box DNA-binding domain, and potential target sequences have been identified. The fos-related antigen 1 (fra-1) gene is closely related to the protooncogene c-fos and encodes a component of transcription factor AP-1. Fra-1 is expressed during spermatogenesis, and the promoter of the rat fra-1 gene contains several potential binding sites for members of the HMG-box family of DNA-binding proteins. We demonstrate that purified SRY protein binds strongly to one of the putative fra-1 HMG-box response elements and that SRY enhances the transcription of rat fra-1 promoter constructs in cotransfection experiments. These results suggest that the function of HMG-box transcription factors may be mediated, in part, by activation of members of the AP-1 transcription factor family.

Transcriptional regulation in the testis: a role for transcription factor AP-1 complexes at various stages of spermatogenesis.

The products of two proto-oncogenes, c-fos and c-jun, have been implicated in signal transduction pathways as regulators of gene expression. Both proto-oncogenes are members of gene families encoding closely related proteins that together make up transcription factor AP-1. The expression of members of this transcription factor has been associated with cellular pathways that result in both mitosis and differentiation. We have been studying the process of spermatogenesis, which is a complex, continual cycle of cell renewal, proliferation and differentiation. Using a seasonal breeder, the European red fox (Vulpes vulpes), as our model, we have examined the expression of five AP-1 family members (c-fos, fra-1, fra-2, c-jun and junB) with a view to elucidating their role in the regulation of spermatogenesis. Unique patterns of expression, falling into three broad categories, were observed for the five genes: (i) continuous expression throughout the spermatogenic cycle (c-fos); (ii) expression only at times corresponding to the onset and shutdown of spermatogenesis (fra-1, fra-2 and c-jun); and (iii) expression only at the onset of the cycle (junB). Furthermore, the proteins were expressed in both premeiotic and post-meiotic cell types, suggesting a role in haploid, as well as diploid, gene expression in this tissue. The data suggest distinct, although not necessarily unrelated, roles for the different components of transcription factor AP-1 in the regulation of spermatogenesis.