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
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Research Support, Non-U.S. Gov't
MeSH terms
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Base Sequence
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Binding Sites
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Cell Line
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Cell Nucleus / physiology*
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DNA / genetics
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DNA / metabolism*
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Dexamethasone / pharmacology*
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HeLa Cells
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Humans
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Methylation
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Microbial Collagenase / genetics
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Molecular Sequence Data
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Oligodeoxyribonucleotides
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Promoter Regions, Genetic
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Protein Biosynthesis
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Proto-Oncogene Proteins c-jun / genetics
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Proto-Oncogene Proteins c-jun / isolation & purification
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Proto-Oncogene Proteins c-jun / metabolism*
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Recombinant Proteins / isolation & purification
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Recombinant Proteins / metabolism
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Restriction Mapping
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Skin
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Tetradecanoylphorbol Acetate / pharmacology*
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Transcription Factors / metabolism*
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Transcription, Genetic* / drug effects
Substances
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Oligodeoxyribonucleotides
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Proto-Oncogene Proteins c-jun
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Recombinant Proteins
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Transcription Factors
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Dexamethasone
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DNA
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Microbial Collagenase
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Tetradecanoylphorbol Acetate