THE ROLE OF PHOSPHATIDYLCHOLINE BIOSYNTHESIS IN THE REGULATION OF THEINO1 GENE OF YEAST

In yeast, as in other eukaryotes, phosphatidylcholine (PC) can be synt hesized via methylation of phosphatidylethanolamine or from free choli ne via the CDP-choline pathway, In yeast, PC biosynthesis is required for the repression of the phospholipid biosynthetic genes, including t he INO1 gene, in response to inositol. In this study, we analyzed the effect of mutations in genes encoding enzymes involved in PC biosynthe sis on the transcriptional regulation of phospholipid biosynthetic gen es. We report that repression of INO1 transcription in response to ino sitol is clearly dependent on ongoing PC biosynthesis, but it is indep endent of the route of synthesis. Our results also suggest that interm ediates in the phosphatidylethanolamine methylation and CDP-choline pa thways are not responsible for generating the regulatory signal that r esults in repression of INO1 and other coregulated genes of phospholip id biosynthesis. Furthermore, repression of INO1 is not tightly correl ated to the proportion of PC in the total cellular phospholipids, Rath er, we report that when the rate of synthesis of PC becomes growth lim iting, the addition of inositol fails to repress the phospholipid bios ynthetic genes, but when the rate of PC synthesis is sufficient to sus tain normal growth, the addition of inositol to the growth medium has the effect of repressing INO1 and other phospholipid biosynthetic gene s.