Control of Ammonium Permease Expression and Filamentous Growth by the GATA Transcription Factors GLN3 and GAT1 in Candida albicans

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Abstract
In response to nitrogen starvation, the human fungal pathogen Candida albicans switches from yeast to filamentous growth. This morphogenetic switch is controlled by the ammonium permease Mep2p, whose expression is induced under limiting nitrogen conditions. In order to understand in more detail how nitrogen starvation-induced filamentous growth is regulated in C. albicans , we identified the cis -acting sequences in the MEP2 promoter that mediate its induction in response to nitrogen limitation. We found that two putative binding sites for GATA transcription factors have a central role in MEP2 expression, as deletion of the region containing these sites or mutation of the GATAA sequences in the full-length MEP2 promoter strongly reduced MEP2 expression. To investigate whether the GATA transcription factors GLN3 and GAT1 regulate MEP2 expression, we constructed mutants of the C. albicans wild-type strain SC5314 lacking one or both of these transcription factors. Expression of Mep2p was strongly reduced in gln3 Δ and gat1 Δ single mutants and abolished in gln3 Δ gat1 Δ double mutants. Deletion of GLN3 strongly inhibited filamentous growth under limiting nitrogen conditions, but the filamentation defect of gln3 Δ mutants could be rescued by constitutive expression of MEP2 from the ADH1 promoter. In contrast, inactivation of GAT1 had no effect on filamentation, and we found that filamentation became independent of the presence of a functional MEP2 gene in the gat1 Δ mutants, indicating that the loss of GAT1 function results in the activation of other pathways inducing filamentous growth. These results demonstrate that the GATA transcription factors GLN3 and GAT1 control expression of the MEP2 ammonium permease and that GLN3 is also an important regulator of nitrogen starvation-induced filamentous growth in C. albicans .