NF-Y behaves as a bifunctional transcription factor that can stimulate or repress the FGF-4 promoter in an enhancer-dependent manner

Cory T. Bernadt, Tamara Nowling, Matthew S Wiebe, A Angie Rizzino

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

NF-Y is a bifunctional transcription factor capable of activating or repressing transcription. NF-Y specifically recognizes CCAAT box motifs present in many eukaryotic promoters. The mechanisms involved in regulating its activity are poorly understood. Previous studies have shown that the FGF-4 promoter is regulated positively by its CCAAT box and NF-Y in embryonal carcinoma (EC) cells where the distal enhancer of the FGF-4 gene is active. Here, we demonstrate that the CCAAT box functions as a negative cis-regulatory element when cis-regulatory elements of the FGF-4 enhancer are disrupted, or after EC cells differentiate and the FGF-4 enhancer is inactivated. We also demonstrate that NF-Y mediates the repression of the CCAAT box and that NF-Y associates with the endogenous FGF-4 gene in both EC cells and EC-differentiated cells. Importantly, we also determined that the orientation and the position of the CCAAT box are critical for its role in regulating the FGF-4 promoter. Together, these studies demonstrate that the distal enhancer of the FGF-4 gene determines whether the CCAAT box of the FGF-4 promoter functions as a positive or a negative cis-regulatory element. In addition, these studies are consistent with NF-Y playing an architectural role in its regulation of the FGF-4 promoter.

Original languageEnglish (US)
Pages (from-to)193-212
Number of pages20
JournalGene Expression
Volume12
Issue number3
StatePublished - Dec 1 2004

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Embryonal Carcinoma Stem Cells
Transcription Factors
Activating Transcription Factors
Genes

Keywords

  • Differentiation
  • EC cells
  • Enhancer
  • F9-differentiated cells
  • Immunoprecipitation
  • NF-Y
  • Transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

NF-Y behaves as a bifunctional transcription factor that can stimulate or repress the FGF-4 promoter in an enhancer-dependent manner. / Bernadt, Cory T.; Nowling, Tamara; Wiebe, Matthew S; Rizzino, A Angie.

In: Gene Expression, Vol. 12, No. 3, 01.12.2004, p. 193-212.

Research output: Contribution to journalArticle

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T1 - NF-Y behaves as a bifunctional transcription factor that can stimulate or repress the FGF-4 promoter in an enhancer-dependent manner

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AU - Nowling, Tamara

AU - Wiebe, Matthew S

AU - Rizzino, A Angie

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AB - NF-Y is a bifunctional transcription factor capable of activating or repressing transcription. NF-Y specifically recognizes CCAAT box motifs present in many eukaryotic promoters. The mechanisms involved in regulating its activity are poorly understood. Previous studies have shown that the FGF-4 promoter is regulated positively by its CCAAT box and NF-Y in embryonal carcinoma (EC) cells where the distal enhancer of the FGF-4 gene is active. Here, we demonstrate that the CCAAT box functions as a negative cis-regulatory element when cis-regulatory elements of the FGF-4 enhancer are disrupted, or after EC cells differentiate and the FGF-4 enhancer is inactivated. We also demonstrate that NF-Y mediates the repression of the CCAAT box and that NF-Y associates with the endogenous FGF-4 gene in both EC cells and EC-differentiated cells. Importantly, we also determined that the orientation and the position of the CCAAT box are critical for its role in regulating the FGF-4 promoter. Together, these studies demonstrate that the distal enhancer of the FGF-4 gene determines whether the CCAAT box of the FGF-4 promoter functions as a positive or a negative cis-regulatory element. In addition, these studies are consistent with NF-Y playing an architectural role in its regulation of the FGF-4 promoter.

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