Identification of a retinoid receptor response element in the human aldehyde dehydrogenase-2 promoter.

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)alpha, beta, and gamma with retinoid X receptor (RXR)alpha 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 RARalpha, when the RAR-specific ligand AM580 was present. Each of the three RXR isoforms alpha, beta, and gamma 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 RXRalpha 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.

• Authors: 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
• Journal: Alcoholism, clinical and experimental research (Alcohol Clin Exp Res) Vol. 27 Issue 12 Pg. 1860-6 (Dec 2003) ISSN: 0145-6008 [Print] England
• PMID: 14691372 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• RARA protein, human
• Rara protein, rat
• Receptors, Retinoic Acid
• Retinoic Acid Receptor alpha
• retinoic acid receptor beta
• ALDH2 protein, human
• Aldehyde Dehydrogenase
• Aldehyde Dehydrogenase, Mitochondrial

Topics

• Aldehyde Dehydrogenase (biosynthesis, genetics)
• Aldehyde Dehydrogenase, Mitochondrial
• Animals
• Cell Line
• Humans
• Mutation
• Promoter Regions, Genetic
• Rabbits
• Rats
• Receptors, Retinoic Acid (analysis, biosynthesis, genetics, metabolism)
• Response Elements (physiology)
• Retinoic Acid Receptor alpha
• Retinoic Acid Receptor gamma