Regulation of gene expression by oxygen in Saccharomyces cerevisiae

Abstract

The oxygen regulation of two broad categories of yeast genes is discussed in this review. The first is made up of genes regulated by heme, and the second is made up of genes whose regulation is heme independent. Heme-regulated genes fall into two classes: heme-activated and heme-repressed genes. Activation is achieved through one of two transcriptional activators, the heme-dependent HAP1 protein or the heme-activated, glucose-repressed HAP2/3/4 complex. Some of the properties and the DNA-binding sites of these activators are discussed. Heme repression is achieved through the action of the ROX1 repressor, the expression of which is transcriptionally activated by heme. Once ROX1 is synthesized, its function is heme independent. Evidence that ROX1 binds to DNA or is part of a DNA-binding complex is described. Factors which modulate the function of these regulatory proteins are discussed, and a schematic of heme activation and repression is presented. The mitochondrial subunits of cytochrome c oxidase are induced by oxygen in a heme-independent fashion. The translation of one, cytochrome c oxidase subunit III, is dependent upon three nucleus-encoded initiation factors. One of these, PET494, is itself translationally regulated by oxygen in a heme-independent fashion. The expression of at least four other mitochondrially encoded cytochrome subunits is dependent upon specific translation factors, raising the potential for translational regulation as a general mechanism. Finally, a number of anaerobic genes that show heme-independent, oxygen-repressed expression have been identified. These fall into two kinetic classes, suggesting that there are at least two different regulatory circuitries.