Transcription factor Sox-2 inhibits co-activator stimulated transcription

Cory T. Bernadt, Tamara Nowling, A Angie Rizzino

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Previous studies have shown that transcription of the fibroblast growth factor-4 (FGF-4) gene by early embryonic cells is dependent upon a powerful distal enhancer located 3 kb downstream of the transcription start site within the untranslated region of the last exon. The transcription factors Sox-2 and Oct-3 cooperatively bind to critical cis-regulatory elements within the enhancer to synergistically activate transcription. Moreover, the co-activator p300 can mediate the synergistic activity of Sox-2 and Oct-3, and p300 associates with the FGF-4 enhancer in vivo. Embryonal carcinoma (EC) cells have been used extensively as a model system to study the regulation of the FGF-4 gene during early development. Recently, it has been suggested that suboptimal levels of Sox-2 expression in F9 EC cells limit the transcription of the FGF-4 gene. The studies presented in this report argue that Sox-2 levels are not limiting in F9 EC cells. Moreover, overexpression of Sox-2 in F9 EC cells decreases FGF-4 promoter activity. In addition, overexpression of Sox-2 in these cells inhibits activation by the co-activators p300, CBP, and OCA-B in a manner that requires the transactivation domain of Sox-2. These findings suggest that Sox-2 levels in F9 EC cells are regulated carefully to avoid interference with the transcription of critical genes.

Original languageEnglish (US)
Pages (from-to)260-267
Number of pages8
JournalMolecular Reproduction and Development
Volume69
Issue number3
DOIs
StatePublished - Nov 1 2004

Fingerprint

Fibroblast Growth Factor 4
Embryonal Carcinoma Stem Cells
Transcription Factors
Genes
Octamer Transcription Factor-2
Untranslated Regions
Transcription Initiation Site
Transcriptional Activation
Exons

Keywords

  • Co-activators
  • EC cells
  • Sox-2
  • Squelching
  • Transcription
  • p300

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Transcription factor Sox-2 inhibits co-activator stimulated transcription. / Bernadt, Cory T.; Nowling, Tamara; Rizzino, A Angie.

In: Molecular Reproduction and Development, Vol. 69, No. 3, 01.11.2004, p. 260-267.

Research output: Contribution to journalArticle

@article{c9e0f94f6702415f8778a1ba902b21f0,
title = "Transcription factor Sox-2 inhibits co-activator stimulated transcription",
abstract = "Previous studies have shown that transcription of the fibroblast growth factor-4 (FGF-4) gene by early embryonic cells is dependent upon a powerful distal enhancer located 3 kb downstream of the transcription start site within the untranslated region of the last exon. The transcription factors Sox-2 and Oct-3 cooperatively bind to critical cis-regulatory elements within the enhancer to synergistically activate transcription. Moreover, the co-activator p300 can mediate the synergistic activity of Sox-2 and Oct-3, and p300 associates with the FGF-4 enhancer in vivo. Embryonal carcinoma (EC) cells have been used extensively as a model system to study the regulation of the FGF-4 gene during early development. Recently, it has been suggested that suboptimal levels of Sox-2 expression in F9 EC cells limit the transcription of the FGF-4 gene. The studies presented in this report argue that Sox-2 levels are not limiting in F9 EC cells. Moreover, overexpression of Sox-2 in F9 EC cells decreases FGF-4 promoter activity. In addition, overexpression of Sox-2 in these cells inhibits activation by the co-activators p300, CBP, and OCA-B in a manner that requires the transactivation domain of Sox-2. These findings suggest that Sox-2 levels in F9 EC cells are regulated carefully to avoid interference with the transcription of critical genes.",
keywords = "Co-activators, EC cells, Sox-2, Squelching, Transcription, p300",
author = "Bernadt, {Cory T.} and Tamara Nowling and Rizzino, {A Angie}",
year = "2004",
month = "11",
day = "1",
doi = "10.1002/mrd.20168",
language = "English (US)",
volume = "69",
pages = "260--267",
journal = "Molecular Reproduction and Development",
issn = "1040-452X",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Transcription factor Sox-2 inhibits co-activator stimulated transcription

AU - Bernadt, Cory T.

AU - Nowling, Tamara

AU - Rizzino, A Angie

PY - 2004/11/1

Y1 - 2004/11/1

N2 - Previous studies have shown that transcription of the fibroblast growth factor-4 (FGF-4) gene by early embryonic cells is dependent upon a powerful distal enhancer located 3 kb downstream of the transcription start site within the untranslated region of the last exon. The transcription factors Sox-2 and Oct-3 cooperatively bind to critical cis-regulatory elements within the enhancer to synergistically activate transcription. Moreover, the co-activator p300 can mediate the synergistic activity of Sox-2 and Oct-3, and p300 associates with the FGF-4 enhancer in vivo. Embryonal carcinoma (EC) cells have been used extensively as a model system to study the regulation of the FGF-4 gene during early development. Recently, it has been suggested that suboptimal levels of Sox-2 expression in F9 EC cells limit the transcription of the FGF-4 gene. The studies presented in this report argue that Sox-2 levels are not limiting in F9 EC cells. Moreover, overexpression of Sox-2 in F9 EC cells decreases FGF-4 promoter activity. In addition, overexpression of Sox-2 in these cells inhibits activation by the co-activators p300, CBP, and OCA-B in a manner that requires the transactivation domain of Sox-2. These findings suggest that Sox-2 levels in F9 EC cells are regulated carefully to avoid interference with the transcription of critical genes.

AB - Previous studies have shown that transcription of the fibroblast growth factor-4 (FGF-4) gene by early embryonic cells is dependent upon a powerful distal enhancer located 3 kb downstream of the transcription start site within the untranslated region of the last exon. The transcription factors Sox-2 and Oct-3 cooperatively bind to critical cis-regulatory elements within the enhancer to synergistically activate transcription. Moreover, the co-activator p300 can mediate the synergistic activity of Sox-2 and Oct-3, and p300 associates with the FGF-4 enhancer in vivo. Embryonal carcinoma (EC) cells have been used extensively as a model system to study the regulation of the FGF-4 gene during early development. Recently, it has been suggested that suboptimal levels of Sox-2 expression in F9 EC cells limit the transcription of the FGF-4 gene. The studies presented in this report argue that Sox-2 levels are not limiting in F9 EC cells. Moreover, overexpression of Sox-2 in F9 EC cells decreases FGF-4 promoter activity. In addition, overexpression of Sox-2 in these cells inhibits activation by the co-activators p300, CBP, and OCA-B in a manner that requires the transactivation domain of Sox-2. These findings suggest that Sox-2 levels in F9 EC cells are regulated carefully to avoid interference with the transcription of critical genes.

KW - Co-activators

KW - EC cells

KW - Sox-2

KW - Squelching

KW - Transcription

KW - p300

UR - http://www.scopus.com/inward/record.url?scp=4744367523&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4744367523&partnerID=8YFLogxK

U2 - 10.1002/mrd.20168

DO - 10.1002/mrd.20168

M3 - Article

C2 - 15349837

AN - SCOPUS:4744367523

VL - 69

SP - 260

EP - 267

JO - Molecular Reproduction and Development

JF - Molecular Reproduction and Development

SN - 1040-452X

IS - 3

ER -