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

Jane Pinaire, Ravishankar Hasanadka, Michelle Fang, Wan Yin Chou, Mark J. Stewart, Wiebe Kruijer, David Crabb

Research output: Contribution to journalArticle

14 Scopus citations

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 RXRα 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. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)192-200
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume380
Issue number1
DOIs
StatePublished - Aug 1 2000

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ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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