A role for MGA2, but not SPT23, in activation of transcription of ERG1 in Saccharomyces cerevisiae.

Abstract The Saccharomyces cerevisiae MGA 2 gene encodes an important regulator of unsaturated fatty acid production, by controlling transcription and mRNA stability of OLE 1, the gene encoding the Δ9 fatty acid desaturase. Lipid composition studies indicated that the mga 2 Δ strain contains elevated relative amounts of squalene when compared to wild-type cells. The deletion of the MGA 2 homologue SPT 23 did not impact squalene levels. To explore the role of MGA 2 in the regulation of sterol synthesis, the transcription of the ERG 1 gene, which encodes squalene epoxidase, was studied using an ERG 1 promoter- lacZ reporter gene construct. We report here that in addition to MGA 2’s role in regulation of unsaturated fatty acids, MGA 2 is required for full basal expression of ERG 1. Mga2p was found to be controlled by a novel regulator in its activation of ERG 1, as neither unsaturated fatty acids nor cobalt affected ERG 1 expression, as had previously been shown for Mga2p’s regulation of OLE 1. Further, response to miconazole treatment, which inhibits production of ergosterol at a later step in the sterol biosynthetic pathway and results in up-regulation of several genes in ergosterol synthesis, was not affected in the mga 2 Δ mutant. In each case, the spt 23 Δ mutant strain shows similar ERG 1 expression to wild-type cells, while the mga 2 Δ / spt 23 Δ strain shows reduced ERG 1 expression, comparable to the mga 2 Δ , suggesting that the role of regulation of ERG 1 transcription is unique to Mga2p.