Genetic and metabolic regulation in yeast

What is it about?

This article describes an example of genetic and metabolic crossregulation in yeast (Saccharomyces cerevisiae), affecting genes of phospholipid biosynthesis and phosphate acquisition. Previous work has shown that genes of phospholipid biosynthesis are efficiently transcribed by the activator complex Ino2 + Ino4 when the precursor molecule inositol is limiting while repressor Opi1 prevents transcription by counteracting Ino2 in the presence of a high concentration of inositol. Similarly, activator Pho4 which is controlled by protein kinase Pho85 stimulates transcription of phosphatase genes when the concentration of free phosphate is low. In contrast, Pho4 becomes deactivated by Pho85-dependent phosphorylation upon supplementation of yeast with phosphate. In this article we show that the availability of phosphate also affects transcription of structural genes of phospholipid biosynthesis and that this crossregulation is mediated by modulation of repressor Opi1. When yeast cells are supplied with high phosphate, sensory protein kinase Pho85 interacts with Opi1 and weakens its repressor function (presumably by phosphorylation), allowing increased biosynthesis of phospholipids. The Pho85 interaction domain within Opi1 overlaps with the domain which is also required for recruitment of the corepressor complex Sin3/Rpd3, providing histone deacetylase activity. This mechanism explains (at least in part) why Pho85 is a positive factor of yeast phospholipid biosynthesis.

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