BINDING AND ACTIVATION OF THE HUMAN ALDEHYDE DEHYDROGENASE-2 PROMOTERBY HEPATOCYTE NUCLEAR FACTOR-4

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is expressed in a tissu e-specific fashion with high levels in liver, heart, kidney, and muscl e, 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 contac ted at motifs containing the hexamer (A)/(G)GGTCA. The 3' site was sho wn to bind in vitro translated HNF-4. It was also shown by electrophor etic mobility shift assay utilizing antibodies against nuclear factors and rat liver nuclear extracts to be bound by hepatocyte nuclear fact or 4 (HNF-4), chicken ovalbumin upstream promoter transcription factor I and II, and retinoid X receptors, A reporter construct containing f our copies of this promoter element was activated by co-transfection o f 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. (C) 1998 Elsevier Science B.V. All rights reserved.