Repeated DNA sequences upstream from HIS1 also occur at several other co-regulated genes in Saccharomyces cerevisiae

The HIS1 gene of Saccharomyces cerevisiae encodes ATP phosphoribosyltransferase, the first enzyme in the pathway of histidine biosynthesis. We have cloned this gene by complementation of a his1 auxotroph. The HIS1 coding region was localized within the cloned segment by assay of subcloned fragments for their ability to complement a his1 auxotroph. We determined the DNA sequence of the HIS1 region defined by this complementation test. S1 nuclease and exonuclease VII mapping of the 5' and 3' termini of HIS1 mRNA reveal considerable heterogeneity at both ends of the transcript, especially the 5' end which displays 13 different termini that span a 110-base pair region. Northern analysis shows that derepression of HIS1 enzyme activity under conditions of amino acid deprivation can be accounted for by an increase in the steady state level of HIS1 mRNA. There are no large differences between the relative levels of HIS1 mRNA molecules with different 5' termini in repressed and derepressed cells. In the DNA sequence upstream from the 5' termini of HIS1 mRNA we have found four closely related copies of a 9-base pair sequence. This sequence is also repeated in the 5' noncoding regions of HIS4, HIS3, and TRP5. Closely related sequences are not found flanking a number of other yeast genes, suggesting that the repeated sequence plays a role in the regulation of amino acid biosynthetic genes subject to the general amino acid control.