Inducible, receptor-dependent protein-DNA interactions at a dioxin-responsive transcriptional enhancer.

M. S. Denison, J. M. Fisher, J. P. Whitlock

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Abstract

We have identified in mouse hepatoma cells a third cis-acting dioxin-responsive element (DRE) within the 5' flanking region of the cytochrome P1-450 gene, which is transcriptionally activated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The DRE can activate a heterologous promoter and functions in either orientation; therefore, it has the properties of a transcriptional enhancer. The DRE fails to activate transcription in receptor-defective cells; therefore, it requires TCDD-receptor complexes for its function. By using a gel retardation assay, we show that nuclear extracts contain a protein that binds to the DRE in TCDD-inducible, receptor-dependent, and DNA sequence-specific fashion. The protein-DNA interaction occurs within 10 min of exposure of the cell to TCDD and does not require ongoing protein synthesis. Our results imply that the TCDD-receptor complex interacts specifically with the DRE and demonstrate a relationship between protein-DNA interaction in vitro and function in vivo. Our findings also suggest that the affinity of the TCDD-receptor complex for the DRE may be relatively high in comparison to analogous protein-DNA interactions at other inducible enhancers.

Original languageEnglish (US)
Pages (from-to)2528-2532
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume85
Issue number8
StatePublished - Apr 1988
Externally publishedYes

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ASJC Scopus subject areas

  • General
  • Genetics

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