Induction of the 4-aminobutyrate and urea-catabolic pathways in Saccharomyces cerevisiae. Specific and common transcriptional regulators.

In the yeast Saccharomyces cerevisiae, induction of the 4-aminobutyrate-catabolic pathway by 4-aminobutyrate requires two positive regulatory factors, encoded by the UGA3 and the UGA35 genes respectively. In addition to this, expression of one gene of this pathway, namely the UGA4 gene encoding the 4-aminobutyrate-specific permease, is controlled negatively by the product of the UGA43 gene [Vissers, S., André, B., Muyldermans, F. & Grenson, M. (1989) Eur. J. Biochem. 181, 357-361]. We show here that the products of two of these regulatory genes, UGA35 and UGA43, also control the expression of the genes encoding the urea-catabolic pathway, although the 4-aminobutyrate and urea-catabolic pathways are synthesised under specific conditions and do not share any enzymatic step or metabolite: the UGA35 pathways are synthesised under specific conditions and do not share any enzymatic step or metabolite: the UGA35 gene is shown to be identical to the DURL gene which was previously identified as a positive regulatory factor of the urea-catabolic pathway; the UGA43 gene product is shown to behave like a negative regulatory factor of this pathway. In contrast to UGA35/DURL and UGA43, the positive regulatory factors encoded by the UGA3 gene and the previously identified DURM gene specifically control 4-aminobutyrate and urea catabolisms respectively. Northern hybridization experiments suggest that the UGA35/DURL and UGA43 common regulatory factors act at the transcriptional level. Our results show that the expression of two biochemically distinct nitrogenous catabolisms, as triggered by their respective inducers, seems to involve multiple regulatory factors, some of which are common to the two catabolic pathways.

Positive and negative regulatory elements control the expression of the UGA4 gene coding for the inducible 4-aminobutyric-acid-specific permease in Saccharomyces cerevisiae.

In Saccharomyces cerevisiae, the pathway of 4-aminobutyric acid catabolism, for use as a nitrogen source, involves a specific permease (encoded by the UGA4 gene) and two enzymes (encoded by the UGA1 and UGA2 genes, respectively). The synthesis of these proteins is induced by 4-aminobutyrate. It also requires the product of the UGA3 gene. Here, we describe four additional regulatory mutations which provide evidence for the existence of both positive and negative regulatory elements which control the final expression of the UGA4 gene. Some of them simultaneously control the expression of the UGA1 and UGA2 genes. Three classes of mutant with a constitutive 4-aminobutyrate-specific permease have been isolated. (a) Recessive mutations in the UGA43 gene suggest that the product of the UGA43 gene behaves like a trans-acting negative regulator of UGA4 gene expression. (b) The semi-dominant mutation (uga11), closely linked to the UGA4 gene, might affect the receptor of the UGA43 gene product. In these two classes of mutant, only the permease is constitutive. (3) The uga81 mutation, closely linked to the UGA3 gene, makes the whole UGA regulon constitutive. On the other hand, recessive mutations at the UGA35 gene locus lead to non-inducibility of the UGA regulon. Hence the UGA35 gene product behaves like a second trans-acting positive regulator in addition to UGA3.