Identification of the copper regulon in Saccharomyces cerevisiae by DNA microarrays.
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.
University of Utah Health Sciences Center, Departments of Medicine and Biochemistry, Salt Lake City, Utah 84132, USA.
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Gross
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Kelleher
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Iyer
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Brown
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Winge
D002352:Carrier Proteins; D003300:Copper / Q000172:deficiency / Q000378:metabolism / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D005800:Genes, Fungal / Q000235:genetics*; D007501:Iron / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D023282:Nuclease Protection Assays; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015719:Single-Strand Specific DNA and RNA Endonucleases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
C500769:CUP1-1 protein, S cerevisiae; C060256:CUP2 protein, S cerevisiae; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C084954:MAC1 protein, S cerevisiae; D009687:Nuclear Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C007121:copper thionein; D003300:Copper; D008668:Metallothionein; D007501:Iron; D015719:Single-Strand Specific DNA and RNA Endonucleases