Gcn4 negatively regulates expression of genes subjected to nitrogen catabolite repression.

It has been considered that three key elements participate in nitrogen catabolite repression (NCR) of Saccharomyces cerevisiae: the GLN3 and GAT1/NIL1-encoded transcriptional activators and their negative regulator Ure2. The fact that expression of various NCR-sensitive genes is not derepressed in the absence of Ure2 has led to the proposition that there must exist a protein with a similar function to that of Ure2. The results presented in this paper show that various NCR-sensitive genes are derepressed through GLN3-mediated transcriptional activation in a gcn4Delta mutant. This effect is additive to that exerted by the lack of Ure2 and to that evoked in rapamycin-treated cultures. Our results uncover the fact that NCR is not solely achieved through the action of Gln3, Gat1, and Ure2. Since Gcn4 regulates the expression of a broad spectrum of genes, the lack of this transcriptional activator could prevent the expression of a potential Gln3 antagonist. Alternatively, Gcn4 could directly hinder Gln3 functioning.