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

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 HNF-4 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.