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Identification of a Retinoid Receptor Response Element in the Human Aldehyde Dehydrogenase‐2 Promoter
Author(s) -
Pinaire Jane,
Chou WanYin,
Morton Michael,
You Min,
Zeng Yan,
Cho Won Kyoo,
Galli Andrea,
Everett Lynn,
Breen Heather,
Dumaual Natividad,
Smith Jennifer R.,
Crabb David
Publication year - 2003
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000100941.86227.4f
Subject(s) - retinoid x receptor , retinoid x receptor alpha , retinoic acid , microbiology and biotechnology , biology , retinoid x receptor gamma , retinoid x receptor beta , retinoic acid receptor , retinoic acid receptor alpha , reporter gene , nuclear receptor , biochemistry , response element , promoter , transcription factor , gene , gene expression
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 RARα, 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.