CIS-ACTING AND TRANS-ACTING ELEMENTS DETERMINING INDUCTION OF THE GENES OF THE GAMMA-AMINOBUTYRATE (GABA) UTILIZATION PATHWAY IN SACCHAROMYCES-CEREVISIAE

In S.cerevisiae, gamma-aminobutyrate (GABA) induces transcription of the UGA genes required for its utilization as a nitrogen source, Analysis of the 5' region of the UGA1 and UGA4 genes led to the identification of a conserved GC-rich sequence (UAS(GABA)) essential to induction by gamma-aminobutyrate, Alone, this UAS(GABA) element also supported some levels of reporter gene transcription in the presence of gamma-aminobutyrate. To be effective, UAS(GABA) requires two positive-acting proteins that both contain a Cys(6)-Zn-2 type zinc-finger motif, namely pathway-specific Uga3p and pleiotropic Uga35p(DaIn81p/DurLp). Further analysis of the UGA4 gene revealed that Gln3p, a global nitrogen regulatory protein containing a GATA zinc-finger domain, is required in order to reach high levels of gamma-aminobutyrate-induced transcription, The Gln3p factor exerts its function mainly through a cluster of 5'-GAT(A/T) A-3'(UAS(GATA)) situated just upstream from UAS(GABA) The role of Gln3p is less predominant in UGA1 than in UGA4 gene expression. We propose that tight coupling between the UAS(GABA) and UAS(GATA) elements enables the cell to integrate, according to its nitrogen status, the induced expression levels of UGA4.