Members of the AP-1 Family of Transcription Factors Regulate the Expression of Gja1 in Mouse GC-1 Spermatogonial Cells

Abstract

Gap junctions, mainly formed by Gja1 (Connexin43), play an essential role in the regulation of proliferation and differentiation of spermatogonia in the testis. Regulation of the abundance of Gja1 in spermatogonia involves various processes, including gene transcription, mRNA maturation, protein synthesis, post-translational modifications, plasma membrane integration and protein degradation. However, gene expression of Gja1 is abnormally decreased in most testicular germ cell tumors. Hence, a better understanding of the mechanisms of transcriptional regulation of Gja1 in spermatogonia is essential to understand how the loss of its expression occurs during the development of testicular cancer. As in other cell types, activator protein-1 (AP-1) transcription factors may be involved in such regulatory process. Thus, AP-1 members were overexpressed in GC-1 cells to assess their impact on Gja1 expression. We showed that Jun and Fosl2 cooperate to activate the Gja1 promoter in GC-1 cells. Furthermore, the recruitment of Jun to the proximal region (−153 to +46 bp) of the Gja1 promoter has been confirmed via chromatin immunoprecipitation. Protein kinase A and calcium-calmodulin protein kinase I also contribute to the activation of Gja1 expression by improving the cooperation between AP-1 factors. Therefore, the reduction in Gja1 expression in testicular germ cell tumors may involve a loss of cooperation between AP-1 factors.

SOX4 exerts contrasting regulatory effects on labor-associated gene promoters in myometrial cells

“…As demonstrated by our results, the addition of SOX4 either on its own or in cooperation with AP-1 factors had regulatory activity at the promoters of known labour associated genes; however, SOX4 did not regulate the Gja1 promoter. This result was surprising at first because Ghouili et al showed SOX and JUN factors can transactivate their targets together; however, our result is consistent with Najih et al who demonstrated the dispensable role of SOX4 on Gja1 promoter activity in spermatogonia GC-1 cells (16,29).…”

SOX4 exerts contrasting regulatory effects on labor-associated gene promoters in myometrial cells

“…As demonstrated by our results, the addition of SOX4 either on its own or in cooperation with AP-1 factors had regulatory activity at the promoters of known labour associated genes; however, SOX4 did not regulate the Gja1 promoter. This result was surprising at first because Ghouili et al showed SOX and JUN factors can transactivate their targets together; however, our result is consistent with Najih et al who demonstrated the dispensable role of SOX4 on Gja1 promoter activity in spermatogonia GC-1 cells [ 16 , 29 ]. Contrarily, SOX4 demonstrated a notable activating effect on the Fos promoter, but only in a cellular context that lacks FOSL2 protein and overexpresses JUND.…”