Metal-sensing transcription factors Mac1p and Aft1p coordinately regulate vacuolar copper transporter CTR2 in Saccharomyces cerevisiae

► Iron depletion induces upregulation of CTR2 transcription which can be abrogated by ablation of AFT1 or MAC1. ► Genetic deletion of either Aft1p or Mac1p removes CTR2 up-regulation induced by copper depletion. ► Exogenous Aft1p cannot upregulate CTR2 transcription in the absence of Mac1p. ► Exogenous Mac1p cannot up-regulate CTR2 transcription in the absence of Aft1p. ► Aft1p and Mac1p form a stable complex and synergistically upregulate CTR2 transcription.