Multiple global regulators control HIS4 transcription in yeast.

Gene expression is dependent on the interaction of DNA binding factors with distinct promoter control elements to activate RNA synthesis. The expression of the HIS4 gene in yeast is under two different control systems. One of these, general amino acid control, involves a DNA binding protein, GCN4, that stimulates transcription in response to amino acid starvation by binding to 5'-TGACTC-3' sequences in the HIS4 promoter region. A second system, the basal level control, stimulates HIS4 transcription in the absence of amino acid starvation. The basal level transcription of the HIS4 gene is under the control of two genes, BAS1 and BAS2, which are also required for the control of purine biosynthesis. In addition, BAS2 is required for the utilization of organic phosphates in the growth medium. Genetic mapping and DNA sequence analysis show that BAS2 is PHO2, a gene previously identified as a regulator of phosphate metabolism. Direct biochemical analysis shows that the BAS2 gene encodes a protein that binds to both the HIS4 and PHO5 promoters. The involvement of a single DNA binding protein in the regulation of histidine, adenine, and phosphate metabolism suggests that yeast may use a few key DNA binding proteins to coordinate the regulation of diverse metabolic pathways.