The transcription factors Junb and Fosl2 cooperate to regulate Cdh3 expression in 15P‐1 Sertoli cells

Abstract In Sertoli cells of the testis, cadherins (Cdh) are important cell‐to‐cell interaction proteins and contribute to the formation of the blood‐testis barrier being essential for germ cells' protection. P‐cadherin or Cdh3 is only expressed in Sertoli cells from embryonic to prepubertal development. Interestingly, the expression profile of Cdh3 correlates with that of activating protein‐1 (AP‐1) transcription factors during Sertoli cells development. To assess their potential implications in the regulation of Cdh3 , different AP‐1 transcription factors were overexpressed in 15P‐1 Sertoli cells. We found that the overexpressions of Junb and Fosl2 activated Cdh3 promoter. ChIP‐qPCR assay and luciferase reporter assay with 5′ promoter deletions and site‐directed mutagenesis confirmed the recruitment of Junb and Fosl2 to an AP‐1 regulatory element at ‐47 bp in the proximal region of Cdh3 promoter in 15P‐1 cells. These findings were further supported by histone modification markers and chromatin accessibility surrounding Cdh3 promoter in mouse testis. Moreover, the knockdowns of Junb and/or Fosl2 by siRNA decreased Cdh3 protein levels. Taken together, these data suggest that in 15P‐1 Sertoli cells, the AP‐1 family members Junb and Fosl2 are responsible for the regulation of Cdh3 expression, which requires the recruitment of both factors to the proximal region of the Cdh3 promoter.