Abstract
We have studied hypoxic induction of transcription by studying the seripauperin (PAU) genes of Saccharomyces cerevisiae. Previous studies showed that PAU induction requires the depletion of heme and is dependent upon the transcription factor Upc2. We have now identified additional factors required for PAU induction during hypoxia, including Hog1, a mitogen-activated protein kinase (MAPK) whose signaling pathway originates at the membrane. Our results have led to a model in which heme and ergosterol depletion alters membrane fluidity, thereby activating Hog1 for hypoxic induction. Hypoxic activation of Hog1 is distinct from its previously characterized response to osmotic stress, as the two conditions cause different transcriptional consequences. Furthermore, Hog1-dependent hypoxic activation is independent of the S. cerevisiae general stress response. In addition to Hog1, specific components of the SAGA coactivator complex, including Spt20 and Sgf73, are also required for PAU induction. Interestingly, the mammalian ortholog of Spt20, p38IP, has been previously shown to interact with the mammalian ortholog of Hog1, p38. Taken together, our results have uncovered a previously unknown hypoxic-response pathway that may be conserved throughout eukaryotes.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Anaerobiosis
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Blotting, Northern
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Blotting, Western
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Ergosterol / metabolism
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Gene Expression Profiling*
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Gene Expression Regulation, Developmental
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Gene Expression Regulation, Fungal
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Heme / metabolism
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Histone Acetyltransferases / genetics
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Histone Acetyltransferases / metabolism
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Membrane Fluidity
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mitogen-Activated Protein Kinases / genetics*
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Mitogen-Activated Protein Kinases / metabolism
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Mutation
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Oligonucleotide Array Sequence Analysis
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Reverse Transcriptase Polymerase Chain Reaction
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae / growth & development
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / genetics*
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Saccharomyces cerevisiae Proteins / metabolism
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism
Substances
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ADA2 protein, S cerevisiae
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MGA2 protein, S cerevisiae
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Membrane Proteins
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PAU1 protein, S cerevisiae
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SSK1 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Trans-Activators
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Transcription Factors
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UPC2 protein, S cerevisiae
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Heme
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GCN5 protein, S cerevisiae
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Histone Acetyltransferases
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Sgf29 protein, S cerevisiae
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Sgf73 protein, S cerevisiae
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HOG1 protein, S cerevisiae
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Mitogen-Activated Protein Kinases
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Ergosterol