The transcription factors SF-1 and SOX8 cooperate to upregulate Cx43 expression in mouse TM4 sertoli cells

Gap junctions made by connexins within the adult testis are essential for communication between Sertoli cells and for spermatogenesis. Sertoli cells play an important role in supporting germ cells differentiation and maturation into spermatozoa. Connexin43 (Cx43) is the most abundant and important connexin of the testis. We have shown previously that the expression of Cx43 is being regulated by SOX and AP-1 transcription factors in Sertoli cells. However, additional regulatory elements being able to recruit orphan nuclear receptors may be involved. Since SOX and SF-1 transcription factors have been shown to cooperate to regulate gene expression in Sertoli cells, we wondered if such mechanism could be involved in the activation of Cx43 expression. Thus, the activity of the Cx43 promoter was measured by co-transfections of luciferase reporter plasmid constructs with different expression vectors for transcription factors in the TM4 Sertoli cell line. The recruitment of SF-1 to the proximal region of the Cx43 promoter was evaluated by chromatin immunoprecipitation. Our results indicate that SOX8 and SF-1, as well as SOX9 and Nur77, cooperate to activate the expression of Cx43 and that SF-1 is being recruited to the -132 to -26 bp region of the Cx43 promoter. These results allow us to have a better understanding of the mechanisms regulating Cx43 expression and could explain some disturbances in communication between Sertoli cells responsible for impaired fertility.