Binding and activation of the human aldehyde dehydrogenase 2 promoter by hepatocyte nuclear factor 4

Mark J. Stewart, Katrina M. Dipple, Mats Estonius, Harikrishna Nakshatri, Lynn M. Everett, David W. Crabb

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is expressed in a tissue- specific fashion with high levels in liver, heart, kidney, and muscle, and low levels in most other tissues. The ALDH2 promoter was found to bind nuclear proteins at a pair of adjacent sites approximately 300 bp upstream from the translation start site, each of which was contacted at motifs containing the hexamer A/GGGTCA. The 3' site was shown to bind in vitro translated HNF-4. It was also shown by electrophoretic mobility shift assay utilizing antibodies against nuclear factors and rat liver nuclear extracts to be bound by hepatocyte nuclear factor 4 (HNF-4), chicken ovalbumin upstream promoter transcription factor I and II, and retinoid X receptors. A reporter construct containing four copies of this promoter element was activated by co-transfection of an HNF4 expression plasmid in COS-1 and hepatoma cell lines. These results suggest that the tissue specificity of ALDH2 expression is in part determined by its activation by HNF-4.

Original languageEnglish (US)
Pages (from-to)181-186
Number of pages6
JournalBiochimica et Biophysica Acta - Gene Structure and Expression
Volume1399
Issue number2-3
DOIs
StatePublished - Aug 20 1998

Keywords

  • Aldehyde dehydrogenase
  • Hepatocyte nuclear factor 4

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Structural Biology
  • Biophysics

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