Effects of histone deacetylase inhibitors on the Ah receptor gene promoter

Patricia M. Garrison, Jane M. Rogers, William R. Brackney, Michael S. Denison

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The aromatic hydrocarbon receptor (AhR) is a ligand-dependent basic helix-loop-helix-PAS-containing transcription factor which is activated by chemicals such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. Constitutive expression of the AhR gene occurs in a tissue- and developmentally specific manner and appears to be altered by chemicals which affect histone deacetylase (HDAC) activity in cells in culture. Here we have directly characterized the effects of two HDAC inhibitors, n-butyrate and trichostatin A, on the promoter activity of the murine AhR gene. HDAC inhibitors increased the constitutive activity of the AhR gene promoter in a luciferase reporter construct by five- to sevenfold in a dose- and time-dependent manner in several cell lines and was correlated with an increase in endogenous AhR activity in an AhR-deficient cell line. Deletion analysis of the upstream region of the AhR gene localized the HDAC inhibitor effect to a 167-bp region encompassing -77 to +90 of the AhR gene promoter. Cotransfection of an AhR promoter-luciferase reporter plasmid with a vector expressing the EIA(12s) oncoprotein, a negative regulator of p300, a protein with histone acetylase activity, decreased AhR promoter activity fivefold. Overall, our results support a role for histone acetylation in the transcriptional activity of the AhR gene promoter. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)161-171
Number of pages11
JournalArchives of Biochemistry and Biophysics
Volume374
Issue number2
DOIs
StatePublished - Feb 15 2000

Keywords

  • Ah receptor
  • Butyrate
  • Histone acetylation
  • Trichostatin A

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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