Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The human alcohol dehydrogenase gene ADH2 is expressed at high levels in liver, at lower levels in kidney and several other tissues, and is not expressed in other tissues such as spleen. This pattern of expression suggests a complex regulatory region that responds to a variety of transcription factors in different cellular contexts. Seven cis-acting sequences in the proximal 271 bp of the ADH2 promoter were mapped. The occupancy of these sites differed markedly among extracts from liver, kidney, spleen, H4IIE-C3 cells, HeLa cells, and CV-1 cells. These differences in occupancy were accompanied by differences in gene expression in the three cell lines. The ADH2 promoter directed substantial CAT expression in H4IIE-C3 cells (rat hepatoma) and in HeLa cells, but only minimal expression in CV-1 cells (monkey kidney fibroblasts). The three cell lines differed in the effects of deletions within the promoter. An ADH2 promoter that contained both the USF/MLTF site and the G3T site gave four- to eight-fold higher expression in both H4IIE-C3 and HeLa cells than a smaller promoter that lacked these sites; in contrast, these sequences did not significantly stimulate transcription in CV-1 cells. A CTF/NF-I-related site acted as a negative element in all three cell lines. Coexpression of C/EBP alpha altered the cell specificity. The ADH2 promoter was moderately stimulated (two-fold) by coexpression of C/EBP alpha in H4IIE-C3 cells, but markedly stimulated in HeLa cells and in CV-1 cells (11- and 20-fold, respectively). These results demonstrate the differential importance of cis-acting sequences and of specific transcription factors in different cells, which allows regulated expression of ADH2 in multiple tissues.
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PMID:Tissue-specific differences in the expression of the human ADH2 alcohol dehydrogenase gene and in binding of factors to cis-acting elements in its promoter. 817 54

Three human alcohol dehydrogenase genes, ADH1, ADH2, and ADH3, were formed by tandem duplications and have diverged in their tissue-specific and developmental expression. Their proximal promoters remain 80-84% identical in sequence, approximately the same degree of identity as at synonymous sites in the coding regions of these three genes. To understand the evolution of tissue specificity, gene expression must be studied in many different cells and tissues. A systematic comparison of their promoters reveals the effects of subtle sequence differences on the binding of nuclear proteins to their cis-acting elements. There are differences in the affinity with which some proteins are bound to altered sites including C/EBP sites, USF/MLTF sites, and the G3T site (which binds Sp1). There are also differences in the sites that are occupied, e.g. CTF/NFI-related sites. These sequence differences are reflected in differences in gene expression in three cell lines. In H4IIE-C3 hepatoma cells, the ADH1 promoter was more active than the ADH2 promoter, and the ADH3 promoter was nearly nonfunctional. In HeLa cells, both ADH1 and ADH2 promoters directed expression; again the ADH3 promoter was extremely weak. None of the three promoters had much activity in CV-1 cells. Coexpression of C/EBP alpha greatly stimulated expression of the ADH1 promoter in HeLa cells and in CV-1 cells, but only weakly stimulated expression in H4IIE-C3 cells. The stimulation of the ADH1 promoter by C/EBP alpha was comparable to that of ADH2, despite the weaker binding to the C/EBP sites that flank the TATA box in ADH1. The ADH3 promoter was not greatly stimulated by C/EBP alpha, despite good binding of C/EBP alpha. These results demonstrate that small differences in the cis-acting elements affect affinity of binding by transcription factors and the pattern of gene expression.
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PMID:Gene expression in a young multigene family: tissue-specific differences in the expression of the human alcohol dehydrogenase genes ADH1, ADH2, and ADH3. 863 48

This review focuses on the regulation of the mammalian medium-chain alcohol dehydrogenase (ADH) genes. This family of genes encodes enzymes involved in the reversible oxidation of alcohols to aldehydes. Interest in these enzymes is increased because of their role in the metabolism of beverage alcohol as well as retinol, and their influence on the risk for alcoholism. There are six known classes ADH genes that evolved from a common ancestor. ADH genes differ in their patterns of expression: most are expressed in overlapping tissue-specific patterns, but class III ADH genes are expressed ubiquitously. All have proximal promoters with multiple cis-acting elements. These elements, and the transcription factors that can interact with them, are being defined. Subtle differences in sequence can affect affinity for these factors, and thereby influence the expression of the genes. This provides an interesting system in which to examine the evolution of tissue specificity. Among transcription factors that are important in multiple members of this gene family are the C/EBPs, Sp1,USF, and AP1, HNF-1, CTF/NF-1, glucocorticoid, and retinoic acid receptors, and several as-yet unidentified negative elements, are important in at least one of the genes. There is evidence that cis-acting elements located far from the proximal promoter are necessary for proper expression. Three of the genes have upstream AUGs in the 5' nontranslated regions of their mRNA, unusual for mammalian genes. The upstream AUGs have been shown to significantly affect expression of the human ADH5 gene.
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PMID:Regulation of the mammalian alcohol dehydrogenase genes. 1069 13