Regulation of hypoxic gene expression in yeast

Baker's yeast, Saccharomyces cerevisiae, can adapt to growth under severe oxygen limitation. Two regulatory systems are described here that control this adaptation. The first involves a heme-dependent repression mechanism. Cells sense hypoxia through the inability to maintain oxygen-dependent heme biosynthesis. Under aerobic conditions, heme accumulates and serves as an effector for the transcriptional activator Hap1. The heme-Hap1 complex activates transcription of the ROX1 gene that encodes a repressor of one set of hypoxic genes. Under hypoxic conditions, heme levels fall, and a heme-deficient Hap1 complex represses ROX1 expression. As a consequence, the hypoxic genes are derepressed. The second regulatory system activates gene expression in response to a variety of stress conditions, including oxygen limitation. Oxygen sensing in this system is heme-independent. The same DNA sequence mediates transcriptional activation of each stress signal.