The retinoid X receptor response element in the human aldehyde dehydrogenase 2 promoter is antagonized by the chicken ovalbumin upstream promoter family of orphan receptors

Arch Biochem Biophys. 2000 Aug 1;380(1):192-200. doi: 10.1006/abbi.2000.1915.

Abstract

Two tandem sites in the aldehyde dehydrogenase 2 promoter (designated FP330-5' and FP330-3') that bind members of the nuclear receptor superfamily were recently identified. Antibodies against apolipoprotein regulatory protein (ARP-1) altered DNA-protein interactions in electrophoretic mobility shift assays using oligonucleotides representing either promoter site and rat liver or cultured cell nuclear extracts. In vitro-translated chicken ovalbumin upstream promoter transcription factor (COUP-TFI), ARP-1, or ErbA-related protein 2 (Ear2) bound both sites. In addition, ARP-1/RXR, COUP-TFI/RXR, and ARP-1/COUP-TFI heterodimers bound the FP330-3' site. Mutagenesis of the FP330-3' site indicated that a DR-1 element was the preferred binding site for these factors. Transfected expression plasmids for these factors suppressed basal expression of reporter constructs containing the FP330-3' sites and the induction of the reporter by RXRalpha plus retinoic acid. Mutation of the two sites increased activity of a construct driven by 600 bp of the ALDH2 promoter in cell lines expressing COUP-TFs. The ALDH2 FP330-3' site appears to represent a complex nuclear receptor response element that is activated by RXRs and HNF-4 but repressed by members of the COUP-TF family.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aldehyde Dehydrogenase / genetics*
  • Aldehyde Dehydrogenase, Mitochondrial
  • Animals
  • Avian Proteins*
  • Binding Sites
  • COUP Transcription Factor I
  • COUP Transcription Factor II
  • COUP Transcription Factors
  • Cell Line
  • Cell Nucleus / metabolism
  • Chickens
  • DNA-Binding Proteins / metabolism
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Liver / metabolism
  • Mutagenesis, Site-Directed
  • Ovalbumin / genetics*
  • Plasmids / metabolism
  • Promoter Regions, Genetic*
  • Protein Binding
  • Rats
  • Receptors, Retinoic Acid / genetics*
  • Receptors, Steroid*
  • Response Elements*
  • Retinoid X Receptors
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Avian Proteins
  • COUP Transcription Factor I
  • COUP Transcription Factor II
  • COUP Transcription Factors
  • DNA-Binding Proteins
  • EAR2 protein, Gallus gallus
  • NR2F1 protein, human
  • NR2F2 protein, human
  • Nr2f1 protein, rat
  • Nr2f2 protein, rat
  • Receptors, Retinoic Acid
  • Receptors, Steroid
  • Retinoid X Receptors
  • Transcription Factors
  • Ovalbumin
  • ALDH2 protein, human
  • Aldehyde Dehydrogenase
  • Aldehyde Dehydrogenase, Mitochondrial