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.
Stewart
M J
MJ
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202-5121, USA.
Dipple
K M
KM
Estonius
M
M
Nakshatri
H
H
Everett
L M
LM
Crabb
D W
DW
D000444:Aldehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology; D008931:Mitochondria, Muscle / Q000201:enzymology; D011401:Promoter Regions, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial