Genome-wide characterization of the Zap1p zinc-responsive regulon in yeast

The Zap1p transcription factor senses cellular zinc status and increases ex pression of its target genes in response to zinc deficiency. Previously kno wn Zap1p-regulated genes encode the Zrt1p, Zrt2p, and Zrt3p zinc transporte r genes and Zap1p itself. To allow the characterization of additional genes in yeast important for zinc homeostasis, a systematic study of gene expres sion on the genome-wide scale was used to identify other Zap1p target genes . Using a combination of DNA microarrays and a computer-assisted analysis o f shared motifs in the promoters of similarly regulated genes, we identifie d 46 genes that are potentially regulated by Zap1p. Zap1p-regulated express ion of seven of these newly identified target genes was confirmed independe ntly by using lacZ reporter fusions, suggesting that many of the remaining candidate genes are also Zap1p targets. Our studies demonstrate the efficac y of this combined approach to define the regulon of a specific eukaryotic transcription factor.