title: Time-Course Analysis of Gene Expression During the Saccharomyces cerevisiae Hypoxic Response.
abstract: Many cells experience hypoxia, or low oxygen, and respond by dramatically altering gene expression. In the yeast Saccharomyces cerevisiae, genes that respond are required for many oxygen-dependent cellular processes, such as respiration, biosynthesis, and redox regulation. To more fully characterize the global response to hypoxia, we exposed yeast to hypoxic conditions, extracted RNA at different times, and performed RNA sequencing (RNA-seq) analysis. Time-course statistical analysis revealed hundreds of genes that changed expression by up to 550-fold. The genes responded with varying kinetics suggesting that multiple regulatory pathways are involved. We identified most known oxygen-regulated genes and also uncovered new regulated genes. Reverse transcription-quantitative PCR (RT-qPCR) analysis confirmed that the lysine methyltransferase EFM6 and the recombinase DMC1, both conserved in humans, are indeed oxygen-responsive. Looking more broadly, oxygen-regulated genes participate in expected processes like respiration and lipid metabolism, but also in unexpected processes like amino acid and vitamin metabolism. Using principle component analysis, we discovered that the hypoxic response largely occurs during the first 2 hr and then a new steady-state expression state is achieved. Moreover, we show that the oxygen-dependent genes are not part of the previously described environmental stress response (ESR) consisting of genes that respond to diverse types of stress. While hypoxia appears to cause a transient stress, the hypoxic response is mostly characterized by a transition to a new state of gene expression. In summary, our results reveal that hypoxia causes widespread and complex changes in gene expression to prepare the cell to function with little or no oxygen.
authors.affiliation: Department of Mathematics, Rowan University, Glassboro, New Jersey 08028.
authors.forename: Nasrine
authors.identifier: 0000-0003-1000-0605
authors.initials: N
authors.lastname: Bendjilali
authors.affiliation: Department of Biological Sciences, Rowan University, Glassboro, New Jersey 08028.
authors.forename: Samuel
authors.initials: S
authors.lastname: MacLeon
authors.affiliation: Department of Chemistry and Biochemistry, Rowan University, Glassboro, New Jersey 08028.
authors.forename: Gurmannat
authors.initials: G
authors.lastname: Kalra
authors.affiliation: Department of Chemistry and Biochemistry, Rowan University, Glassboro, New Jersey 08028.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Willis
authors.affiliation: Department of Chemistry and Biochemistry, Rowan University, Glassboro, New Jersey 08028.
authors.forename: A K M Nawshad
authors.initials: AK
authors.lastname: Hossian
authors.affiliation: Department of Chemistry and Biochemistry, Rowan University, Glassboro, New Jersey 08028.
authors.forename: Erica
authors.initials: E
authors.lastname: Avery
authors.affiliation: Department of Chemistry and Biochemistry, Rowan University, Glassboro, New Jersey 08028.
authors.forename: Olivia
authors.initials: O
authors.lastname: Wojtowicz
authors.affiliation: Department of Biological Sciences, Rowan University, Glassboro, New Jersey 08028 hickmanm@rowan.edu.|Department of Chemistry and Biochemistry, Rowan University, Glassboro, New Jersey 08028.
authors.forename: Mark J
authors.identifier: 0000-0003-3643-8023
authors.initials: MJ
authors.lastname: Hickman
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics*; D015687:Cell Hypoxia / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015966:Gene Expression Regulation, Fungal; D059647:Gene-Environment Interaction; D006801:Humans; D008780:Methyltransferases / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010100:Oxygen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D017423:Sequence Analysis, RNA; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; C513033:DMC1 protein, S cerevisiae; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C000607381:Efm6 protein, S cerevisiae; D008780:Methyltransferases; D010100:Oxygen
keywords: anaerobic; mRNA; metabolism; signaling; transcriptome