Identification of a Retinoid Receptor Response Element in the Human Aldehyde Dehydrogenase-2 Promoter

Jane Pinaire, Wan Yin Chou, Michael Morton, Min You, Yan Zeng, Won Kyoo Cho, Andrea Galli, Lynn Everett, Heather Breen, Natividad Dumaual, Jennifer R. Smith, David Crabb

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background: The human aldehyde dehydrogenase-2 promoter contains sites that bind members of the nuclear receptor family, and one (designated FP330-3′) is predicted to bind retinoic acid receptors. Methods: Binding of retinoid receptors to the FP330-3′ oligonucleotide duplex and point mutations thereof was assayed using electrophoretic mobility shift assays. The function of the promoter element was determined in transfection assays. Results: Heterodimers of retinoic acid receptor (RAR)α, β, and γ with retinoid X receptor (RXR)α bound the FP330-3′ site. Mutagenesis of the FP330-3′ site suggested that either the upstream DR-5 or downstream DR-1 could mediate binding of RAR/RXR. FP330-3′ oligonucleotide duplexes were not bound by in vitro translated RXR homodimers but weakly competed with a synthetic DR-1 oligonucleotide duplex for binding by RXR. A reporter construct carrying four copies of the FP330-3′ element was induced by cotransfection of rat hepatoma cells with a construct encoding RARa, when the RAR-specific ligand AM580 was present. Each of the three RXR isoforms α, β, and γ stimulated the expression of reporter constructs containing the FP330-3′ sites in a 9-cis retinoic acid-dependent fashion in cells in culture. This was confirmed in the case of RXRα using the RXR-specific ligand methoprene. Conclusion: The human aldehyde dehydrogenase-2 promoter contains a retinoid response element, which may contribute to regulation of the gene.

Original languageEnglish (US)
Pages (from-to)1860-1866
Number of pages7
JournalAlcoholism: Clinical and Experimental Research
Volume27
Issue number12
DOIs
StatePublished - Dec 2003

Keywords

  • Aldehyde Dehydrogenase
  • Liver
  • Receptor
  • Retinoic Acid
  • Transcription
  • Vitamin A

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

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    Pinaire, J., Chou, W. Y., Morton, M., You, M., Zeng, Y., Cho, W. K., Galli, A., Everett, L., Breen, H., Dumaual, N., Smith, J. R., & Crabb, D. (2003). Identification of a Retinoid Receptor Response Element in the Human Aldehyde Dehydrogenase-2 Promoter. Alcoholism: Clinical and Experimental Research, 27(12), 1860-1866. https://doi.org/10.1097/01.ALC.0000100941.86227.4F