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, A Angie Rizzino

Research output: Contribution to journalArticle

12 Citations (Scopus)

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

Fingerprint

Growth Factor Receptors
Transforming Growth Factors
Transcription Factors
Embryonal Carcinoma Stem Cells
Transcription Initiation Site
Response Elements
Reporter Genes
Genes
Messenger RNA

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Stimulation of the murine type II transforming growth factor-β receptor promoter by the transcription factor Egr-1. / Wilder, Phillip J.; Bernadt, Cory T.; Kim, Jae Hwan; Rizzino, A Angie.

In: Molecular Reproduction and Development, Vol. 63, No. 3, 01.11.2002, p. 282-290.

Research output: Contribution to journalArticle

@article{deb975ff86974b6ba3e2288317cf6a6c,
title = "Stimulation of the murine type II transforming growth factor-β receptor promoter by the transcription factor Egr-1",
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.",
keywords = "Early growth response-1, Embryonal carcinoma cells, Gene regulation, Transforming growth factor-β-receptor",
author = "Wilder, {Phillip J.} and Bernadt, {Cory T.} and Kim, {Jae Hwan} and Rizzino, {A Angie}",
year = "2002",
month = "11",
day = "1",
doi = "10.1002/mrd.10165",
language = "English (US)",
volume = "63",
pages = "282--290",
journal = "Molecular Reproduction and Development",
issn = "1040-452X",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Stimulation of the murine type II transforming growth factor-β receptor promoter by the transcription factor Egr-1

AU - Wilder, Phillip J.

AU - Bernadt, Cory T.

AU - Kim, Jae Hwan

AU - Rizzino, A Angie

PY - 2002/11/1

Y1 - 2002/11/1

N2 - 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.

AB - 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.

KW - Early growth response-1

KW - Embryonal carcinoma cells

KW - Gene regulation

KW - Transforming growth factor-β-receptor

UR - http://www.scopus.com/inward/record.url?scp=0036836544&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036836544&partnerID=8YFLogxK

U2 - 10.1002/mrd.10165

DO - 10.1002/mrd.10165

M3 - Article

VL - 63

SP - 282

EP - 290

JO - Molecular Reproduction and Development

JF - Molecular Reproduction and Development

SN - 1040-452X

IS - 3

ER -