Wnt/β-catenin signaling enhances transcription of the CX43 gene in murine Sertoli cells

Sertoli cells provide the nutritional and metabolic support for germ cells. Wnt/beta-catenin signaling is important for the development of the seminiferous epithelium during embryonic age, although after birth this pathway is downregulated. Cx43 gene codes for a protein that is critical during testicular development. The Cx43 promoter contains TCF/beta-catenin binding elements (TBEs) that contribute CX43 expression in different cell types and which may also be regulating the expression of this gene in Sertoli cells. In this study, we demonstrate that 42GPA9 Sertoli cells respond to treatments that result in accumulation of beta-catenin within the nucleus and in upregulation of CX43 gene transcription. beta-Catenin binds to TBEs located both upstream and downstream of the transcriptional start site (TSS). Luciferase reporter experiments revealed that TBEs located upstream of the TSS are necessary for beta-catenin-mediated upregulation. Our results also indicate that the Wnt/beta-catenin-dependent upregulation of the Cx43 gene in Sertoli cells is accompanied by changes in epigenetic parameters that may be directly contributing to generating a chromatin environment that facilitates the establishment of the transcriptional machinery at this promoter.