A copper transcription factor, AfMac1, regulates both iron and copper homeostasis in the opportunistic fungal pathogen .

Although iron and copper are co-ordinately regulated in living cells, the homeostatic effects of each of these metals on the other remain unknown. Here, we show the function of AfMac1, a transcriptional activator of the copper and iron regulons of , on the interaction between iron and copper. In addition to the copper-specific AfMac1-binding motif 5'-TGT-3' found in the promoter region of , the iron-specific AfMac1-binding motif 5'-(C/G)NN(A/T)(A/C)-3' was identified in the iron regulon but not in the copper regulon by ChIP sequence analysis. Furthermore, mutation of the AfMac1-binding motif of eliminated AfMac1-mediated up-regulation. Interestingly, the regulation of gene expression in the iron regulon by AfMac1 was not affected by copper and AfMac1 localized to the nucleus under iron- or copper-depleted conditions, and AfMac1 was mostly detected in the cytoplasm under iron- or copper-replete conditions Taken together, these results suggest that independently regulates iron and copper homeostasis in a manner that involves AfMac1 and mutual interactions.