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Stimulation of the murine type II transforming growth factor‐β receptor promoter by the transcription factor Egr‐1
Author(s) -
Wilder Phillip J.,
Bernadt Cory T.,
Kim JaeHwan,
Rizzino Angie
Publication year - 2002
Publication title -
molecular reproduction and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 105
eISSN - 1098-2795
pISSN - 1040-452X
DOI - 10.1002/mrd.10165
Subject(s) - biology , transcription factor , microbiology and biotechnology , promoter , caat box , reporter gene , negative regulatory element , response element , gene , transcription (linguistics) , regulatory sequence , gene expression , genetics , linguistics , philosophy
Previous studies have demonstrated that differentiation of murine embryonal carcinoma (EC) cells leads to the appearance of high affinity receptors for transforming growth factor‐β (TGF‐β). Subsequently, it was demonstrated that differentiation of F9 EC cells leads to increases in the transcription of the type II TGF‐β‐receptor gene ( TβR‐II ) and leads to significant increases in the steady‐state levels of TβR‐II mRNA. Analysis of the human TβR‐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 TβR‐II promoter. We have identified an Egr‐1 response‐element ∼150 bp upstream of the major transcription start site of the murine TβR‐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 TβR‐II promoter. In contrast to a previous report, which reported that Egr‐1 inhibits expression of human TβR‐II promoter/reporter gene constructs, we did not observe an inhibitory effect of Egr‐1 that was specific for the human TβR‐II promoter. Taken together, the findings described in this report identify important differences between the human and the murine TβR‐II promoter, and our findings identify an Egr‐1 cis ‐regulatory element that is capable of stimulating the activity of the murine TβR‐II promoter. Mol. Reprod. Dev. 63: 282–290, 2002. © 2002 Wiley‐Liss, Inc.