Recruitment of Tup1p and Cti6p regulates heme-deficient expression of Aft1p target genes

In the budding yeast Saccharomyces cerevisiae, transcription of genes encoding for the high-affinity iron (FET3, FTR1) and copper (CTR1) transporters does not occur in the absence of heme. We show that the Aft1p binding region of the FET3 promoter or the Mac1p binding region of the CTR1 promoter is necessary and sufficient to mediate heme-deficient repression. Transcription is repressed in the absence of heme, and a genetic screen identified Tup1p and Hda1p as being required for transcriptional repression. In contrast to FET3 and CTR1, Aft1p target genes ARN1 and FIT1 are transcribed in the absence of heme. A 14 bp sequence in the ARN1 promoter is necessary and sufficient to permit transcription in the absence of heme. Transcription in the absence of heme required the presence of Cti6p to overcome the effect of Tup1p, and Cti6p was recruited to the ARN1 promoter in the absence of heme. We hypothesize that transcription of the siderophore transporter ARN1 permits yeast to accumulate iron in the absence of oxygen and to deny iron to competing organisms.