Stimulation of the murine type II transforming growth factor-β receptor promoter by the transcription factor Egr-1

Phillip J. Wilder, Cory T. Bernadt, Jae Hwan Kim, Angie Rizzino

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)282-290
Number of pages9
JournalMolecular Reproduction and Development
Volume63
Issue number3
DOIs
StatePublished - Nov 1 2002

Keywords

  • Early growth response-1
  • Embryonal carcinoma cells
  • Gene regulation
  • Transforming growth factor-β-receptor

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology
  • Cell Biology

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