Hormonal regulation of the rat class I alcohol dehydrogenase gene.

Expression of the rat liver (class I) alcohol dehydrogenase gene is regulated by hormones. Potential nuclear transcription factors of the rat class I alcohol dehydrogenase gene were identified. Proteins from rat liver nuclear extracts were found to bind to the alcohol dehydrogenase promoter at regions 1, 2, and 3, corresponding to positions -2 to -18, -36 to -44, and -52 to -60, relative to the start site of transcription. Region 1 was found to be bipartite and to interact with both the CCAAT/enhancer binding protein (C/EBP) and the liver activator protein (LAP) between position -10 and -22, while a different protein designated EDBP (for Enhancer-site Downstream Binding Protein) bound between position -1 and -10, a sequence previously not known to interact with any transcription factors. Region 2 has the sequence 5' CACCC-'3; binding to this sequence has been shown to act cooperatively with binding of the glucocorticoid binding site in the activation of various genes. The upstream stimulatory factor (USF) binds to region 3. C/EBP, LAP, and USF were all found to activate the alcohol dehydrogenase promoter in cotransfection experiments. It is postulated that one or more of these nuclear factors may mediate hormonal effects on the alcohol dehydrogenase gene.