Stimulation of the murine type II transforming growth factor-beta receptor promoter by the transcription factor Egr-1.Mol Reprod Dev. 2002 Nov; 63(3):282-90.MR
Previous studies have demonstrated that differentiation of murine embryonal carcinoma (EC) cells leads to the appearance of high affinity receptors for transforming growth factor-beta (TGF-beta). Subsequently, it was demonstrated that differentiation of F9 EC cells leads to increases in the transcription of the type II TGF-beta-receptor gene (TbetaR-II) and leads to significant increases in the steady-state levels of TbetaR-II mRNA. Analysis of the human TbetaR-II promoter in F9-differentiated cells identified several cis-regulatory elements that influence the activity of the promoter, including a CRE/ATF site and a CCAAT box motif. In the work described in this report, we focused on the effect of the transcription factor Egr-1 on the murine TbetaR-II promoter. We have identified an Egr-1 response-element approximately 150 bp upstream of the major transcription start site of the murine TbetaR-II gene. We demonstrate by electrophoretic mobility shift analysis (EMSA) that this cis-regulatory element binds Egr-1, and we demonstrate that disruption of this site eliminates the response to Egr-1. As part of this analysis, we also examined the effect of Egr-1 on human TbetaR-II promoter. In contrast to a previous report, which reported that Egr-1 inhibits expression of human TbetaR-II promoter/reporter gene constructs, we did not observe an inhibitory effect of Egr-1 that was specific for the human TbetaR-II promoter. Taken together, the findings described in this report identify important differences between the human and the murine TbetaR-II promoter, and our findings identify an Egr-1 cis-regulatory element that is capable of stimulating the activity of the murine TbetaR-II promoter.