The 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 arc six known classes of ADH genes that evolved from a common ancestor. ADH genes differ in their patterns of expression: most arc expressed in overlapping tissue-specific patterns, but class III ADH genes arc expressed ubiquitously. All have proximal promoters with multiple cis-acting elements. These elements, and the transcription factors that can interact with them, arc 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 arc important in multiple members of this gene family arc the C/EBPs, Sp1, USF, and AP1. HNF-1, CTF/NF-I, glucocorticoid, and retinoic acid receptors, and several as-yet unidentified negative elements, arc important in at least one of the genes. There is evidence that cis-acting elements located far from the proximal promoter arc 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.
|Number of pages||47|
|Journal||Progress in Nucleic Acid Research and Molecular Biology|
|State||Published - 2000|
ASJC Scopus subject areas
- Molecular Biology