Metabolic-state-dependent remodeling of the transcriptome in response to anoxia and subsequent reoxygenation in Saccharomyces cerevisiae.
We conducted a comprehensive genomic analysis of the temporal response of yeast to anaerobiosis (six generations) and subsequent aerobic recovery ( approximately 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 <or=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 approximately 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 (>or=2 generations) with the activation of Upc2- and Mot3-regulated networks involved in sterol and cell wall homeostasis. The response to reoxygenation was rapid (<5 min) and similar in both media, dominated by Yap1 networks involved in oxidative stress/redox regulation and the concomitant activation of heme-regulated ones. Our analyses revealed extensive networks of genes subject to combinatorial regulation by both heme-dependent (e.g., Hap1, Hap2/3/4/5, Rox1, Mot3, and Upc2) and heme-independent (e.g., Yap1, Skn7, and Puf3) factors under these conditions. We also uncover novel functions for several cis-regulatory sites and trans-acting factors and define functional regulons involved in the physiological acclimatization to changes in oxygen availability.
Lai
Liang-Chuan
LC
Department of Molecular and Integrative Physiology, University of Illinois, 524 Burrill Hall, 407 S. Goodwin Ave., Urbana, 61801, USA.
Kosorukoff
Alexander L
AL
Burke
Patricia V
PV
Kwast
Kurt E
KE
D000693:Anaerobiosis; D016000:Cluster Analysis; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005690:Galactose / Q000494:pharmacology; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D005947:Glucose / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D005947:Glucose; D010100:Oxygen; D005690:Galactose