In Saccharomyces cerevisiae, copper ions regulate gene expression through the 
two transcriptional activators, Ace1 and Mac1. Ace1 mediates copper-induced gene 
expression in cells exposed to stressful levels of copper salts, whereas Mac1 
activates a subset of genes under copper-deficient conditions. DNA microarray 
hybridization experiments revealed a limited set of yeast genes differentially 
expressed under growth conditions of excess copper or copper deficiency. Mac1 
activates the expression of six S. cerevisiae genes, including CTR1, CTR3, FRE1, 
FRE7, YFR055w, and YJL217w. Two of the last three newly identified Mac1 target 
genes have no known function; the third, YFR055w, is homologous to cystathionine 
gamma-lyase encoded by CYS3. Several genes that are differentially expressed in 
cells containing a constitutively active Mac1, designated Mac1(up1), are not 
direct targets of Mac1. Induction or repression of these genes is likely a 
secondary effect of cells because of constitutive Mac1 activity. Elevated copper 
levels induced the expression of the metallothioneins CUP1 and CRS5 and two 
genes, FET3 and FTR1, in the iron uptake system. Copper-induced FET3 and FTR1 
expression arises from an indirect copper effect on cellular iron pools.