Interference between pathway-specific transcription factors: glucocorticoids antagonize phorbol ester-induced AP-1 activity without altering AP-1 site occupation in vivo

EMBO J. 1992 Jun;11(6):2241-6.

Abstract

Phorbol esters stimulate and glucocorticoid hormones down-regulate a variety of promoters such as that of the collagenase gene through the transcription factor AP-1 (Fos/Jun). We now show by genomic footprinting of the collagenase promoter that phorbol ester treatment of cells results in the binding of AP-1 to its cognate DNA binding site in vivo. The DNA-protein contacts obtained in living cells are also found in vitro using cloned DNA and purified AP-1. Although in vitro synthesized glucocorticoid receptor can disturb the DNA binding of Jun homodimers, it does not interfere with the binding of Fos-Jun heterodimers or of purified AP-1 in vitro. Consistently, fully inhibitory doses of glucocorticoid hormone cause no change in apparent occupation of the AP-1 binding site in vivo. The hormone receptor acts without itself binding to DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Cell Line
  • Cell Nucleus / physiology*
  • DNA / genetics
  • DNA / metabolism*
  • Dexamethasone / pharmacology*
  • HeLa Cells
  • Humans
  • Methylation
  • Microbial Collagenase / genetics
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides
  • Promoter Regions, Genetic
  • Protein Biosynthesis
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / isolation & purification
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Restriction Mapping
  • Skin
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Transcription Factors / metabolism*
  • Transcription, Genetic* / drug effects

Substances

  • Oligodeoxyribonucleotides
  • Proto-Oncogene Proteins c-jun
  • Recombinant Proteins
  • Transcription Factors
  • Dexamethasone
  • DNA
  • Microbial Collagenase
  • Tetradecanoylphorbol Acetate