title: 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.
  
  
  CONCLUSIONS
  The human aldehyde dehydrogenase-2 promoter contains a retinoid response element, which may contribute to regulation of the gene.
authors.affiliation: Department of Medicine, Indiana University School of Medicine and Veterans Affairs Medical Center, Indianapolis, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Pinaire
authors.forename: Wan-Yin
authors.initials: WY
authors.lastname: Chou
authors.forename: Michael
authors.initials: M
authors.lastname: Morton
authors.forename: Min
authors.initials: M
authors.lastname: You
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
authors.forename: Won Kyoo
authors.initials: WK
authors.lastname: Cho
authors.forename: Andrea
authors.initials: A
authors.lastname: Galli
authors.forename: Lynn
authors.initials: L
authors.lastname: Everett
authors.forename: Heather
authors.initials: H
authors.lastname: Breen
authors.forename: Natividad
authors.initials: N
authors.lastname: Dumaual
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Smith
authors.forename: David
authors.initials: D
authors.lastname: Crabb
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D002460:Cell Line; D006801:Humans; D009154:Mutation; D011401:Promoter Regions, Genetic; D011817:Rabbits; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000502:physiology*; D000072482:Retinoic Acid Receptor alpha; D000097768:Retinoic Acid Receptor gamma
chemical_list: D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D000097768:Retinoic Acid Receptor gamma; C000607071:RARA protein, human; C000607073:Rara protein, rat; C082925:retinoic acid receptor beta; C096127:ALDH2 protein, human