Cytochrome c oxidase from Saccharomyces cerevisiae is subject to intricate control at the level of transcription of the various genes encoding its subunits. Expression of the subunit VI encoding gene, COX6, is glucose repressed, growth phase induced, and dependent on oxygen and heme availability. An upstream activation region for COX6, UAS6, was found to contain a glucose responsive region, a heme dependent region (HDS1), and a binding site for the transcription factor, BAF1. BAF1 was the only factor observed to form a protein complex with UAS6 in vitro. However, we found that binding of BAF1 was unaffected by oxygen or heme regulation. In the present communication, we have identified a DNA binding activity that was growth phase induced and dependent on oxygen and heme availability. This highly regulated activity was detected by its discrete binding to the heme responsive site, HDS1, in UAS6. Nonetheless, it appears to have weak DNA binding specificity. (C) 1995 Academic Press, Inc.