AP-1 binds to a putative cAMP response element of the MyoD1 promoter and negatively modulates MyoD1 expression in dividing myoblasts

Gustavo Pedraza-Alva, Jean Marc Zingg, Jean Pierre Jost

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

We have studied the transcriptional activity of the mouse MyoD1 gene promoter in vivo and in vitro using mouse G8 myoblasts and muscle cell nuclear extracts. 5' deletion analysis of the promoter and transcription- competition analysis using oligonucleotides corresponding to several cis- acting elements revealed that the basal activity of the MyoD1 promoter is conferred by two SP1 boxes, an AP-2 box, and a CAAT box. We have identified a negative regulatory sequence located between nucleotide position -342 to - 322 with respect to the cap site. The negative regulatory element shows sequence homology with cAMP-responsive element (CRE) and AP-1 binding site (5'-GAGCACTGAGGTCAGTACAG-3'). As determined by gel mobility shift competition analysis, oligonucleotides containing AP-1 binding sites inhibit protein interactions with the MyoD1 CRE-like element. We also show that binding to this element is down-regulated during myogenic differentiation and can be reinduced by the addition of serum. Furthermore, mutation of the CRE-like element induces MyoD promoter activity in diving myoblasts. By using anti-c- Fos antibodies we show that AP-1 is binding to the MyoD1 CRE-like element. Our results indicate that AP-1 negatively modulates MyoD1 expression in growing myoblasts and strongly suggest that c-Fos and c-Jun inhibit myogenesis and MyoD1 expression by direct binding to a negative cis-acting element in the MyoD1 promoter.

Original languageEnglish (US)
Pages (from-to)6978-6985
Number of pages8
JournalJournal of Biological Chemistry
Volume269
Issue number9
StatePublished - Mar 4 1994
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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