Metabolic-State-Dependent Remodeling of the Transcriptome in Response to Anoxia and Subsequent Reoxygenation in Saccharomyces cerevisiae

Abstract

We conducted a comprehensive genomic analysis of the temporal response of yeast to anaerobiosis (six generations) and subsequent aerobic recovery (≈2 generations) to reveal metabolic-state (galactose versus glucose)-dependent differences in gene network activity and function. Analysis of variance showed that far fewer genes responded (raw P value of ≤10 ⁻⁸ ) to the O ₂ shifts in glucose (1,603 genes) than in galactose (2,388 genes). Gene network analysis reveals that this difference is due largely to the failure of “stress”-activated networks controlled by Msn2/4, Fhl1, MCB, SCB, PAC, and RRPE to transiently respond to the shift to anaerobiosis in glucose as they did in galactose. After ≈1 generation of anaerobiosis, the response was similar in both media, beginning with the deactivation of Hap1 and Hap2/3/4/5 networks involved in mitochondrial functions and the concomitant derepression of Rox1-regulated networks for carbohydrate catabolism and redox regulation and ending (≥2 generations) with the activation of Upc2- and Mot3-regulated networks involved in sterol and cell wall homeostasis. The response to reoxygenation was rapid (cis -regulatory sites and trans -acting factors and define functional regulons involved in the physiological acclimatization to changes in oxygen availability.