For a large number of oxygen-regulated genes in the facultative aerobe, Saccharomyces cerevisiae, the presence of oxygen is sensed through the ability to use oxygen for heme biosynthesis. Heme induces the transcription of oxygen-induced genes and represses the transcription of hypoxic genes. Repression is mediated by the Rox1 protein in conjunction with the Ssn6/Tup1 general repression complex. The differential repression of hypoxic genes results from a combination of the tightness of Rox1 binding to the regulatory region of specific hypoxic genes and the presence or absence of binding sites for Mot3 which enhances Rox1 repression.