Identification and characterization of a novel progesterone receptor-binding element in the mouse prostaglandin E receptor subtype EP2 gene

Background: Gene expression of prostaglandin E receptor EP2 is induced in the luminal epithelium of the mouse uterus during peri-implantation period (day-5 of pseudopregnancy), suggesting the involvement of progesterone and its receptor (PR) in this expression. However it remains unclear whether PR affects EP2 gene expression through its binding. Results: We investigated transcriptional regulation of EP2 gene expression with reporter gene analysis using HeLa cells with or without expression of the PR. The 5′-flanking region (-3260 to -27, upstream of the translation initiation site) exhibited progesterone-induced promoter activation and basal promoter activity in the presence of PR. Using successive deletion analysis, we determined the six regulatory regions in the EP2 gene. Three regions were found to be involved in progesterone-induced promoter activation, whereas the other three regions were involved in basal promoter activity in the presence of PR. We identified a novel PR-binding sequence, 5′-G(G/A)CCGGA-3′, in the two basal promoter regions and Sp1- and Sp3-binding in the other basal promoter region. Conclusions: We identified a novel PR-binding sequence, which may be involved in the regulation of basal promoter activity in the EP2 gene.