The co-activator p300 associates physically with and can mediate the action of the distal enhancer of the FGF-4 gene

Tamara Nowling, Cory Bernadt, Lance Johnson, Michelle Desler, A Angie Rizzino

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Distal enhancers commonly regulate gene expression. However, the mechanisms of transcriptional mediation by distal enhancers remain largely unknown. To better understand distal enhancer-mediated transcription, we examined the regulation of the FGF-4 gene. The FGF-4 gene is regulated during early development by a powerful distal enhancer located downstream of the promoter in exon 3. Sox-2 and Oct-3 bind to the enhancer and are required for the activation of the FGF-4 gene. Previously, we implicated the co-activator p300 as a mediator of Sox-2/Oct-3 synergistic activation of a heterologous promoter, suggesting that p300 may play a role in mediating enhancer activation of the FGF-4 gene. In this study, we provide both functional and physical evidence that p300 plays an important role in the action of the FGF-4 enhancer. Specifically, we show that E1a, but not a mutant form of E1a that is unable to bind p300, inhibits enhancer activation of the FGF-4 promoter. We also demonstrate that Gal4/p300 fusion proteins can stimulate the FGF-4 promoter when bound to the FGF-4 enhancer. Additionally, we present evidence that p300 mediation of the FGF-4 enhancer requires acetyltransferase activity. Importantly, we also show that Sox-2 and p300 are physically associated with the endogenous FGF-4 enhancer but weakly associated with the endogenous FGF-4 promoter. These results are consistent with a model of transitory interaction between the distal enhancer and the FGF-4 promoter. Our results also suggest that intragenic distal enhancers may use mechanisms that differ from extragenic distal enhancers.

Original languageEnglish (US)
Pages (from-to)13696-13705
Number of pages10
JournalJournal of Biological Chemistry
Volume278
Issue number16
DOIs
StatePublished - Apr 18 2003

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Genes
Chemical activation
Acetyltransferases
Transcription
Gene expression
Exons
Fusion reactions
Gene Expression
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

The co-activator p300 associates physically with and can mediate the action of the distal enhancer of the FGF-4 gene. / Nowling, Tamara; Bernadt, Cory; Johnson, Lance; Desler, Michelle; Rizzino, A Angie.

In: Journal of Biological Chemistry, Vol. 278, No. 16, 18.04.2003, p. 13696-13705.

Research output: Contribution to journalArticle

Nowling, Tamara ; Bernadt, Cory ; Johnson, Lance ; Desler, Michelle ; Rizzino, A Angie. / The co-activator p300 associates physically with and can mediate the action of the distal enhancer of the FGF-4 gene. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 16. pp. 13696-13705.
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