| Citation | Shen C, Nettleton D, Jiang M, Kim SK, Powell-Coffman JA. Roles of the HIF-1 hypoxia-inducible factor during hypoxia response in Caenorhabditis elegans. J Biol Chem, 2005. |
| PubMed ID | 15781453 |
| Short Description | Roles of the HIF-1 hypoxia-inducible factor during hypoxia response in Caenorhabditis elegans. GEO Record: GSE2836 Platform: GPL2569 Download gene-centric, log2 transformed data: WBPaper00026596.ce.mr.csv |
| # of Conditions | 9 |
Full Description
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The human hypoxia inducible transcription factor HIF-1 is a critical regulator of cellular and systemic responses to low oxygen levels. When oxygen levels are high, the HIF-1 alpha subunit is hydroxylated and is targeted for degradation by the von Hippel-Lindau tumor suppressor protein (VHL). This regulatory pathway is evolutionarily conserved, and the C. elegans hif-1 and vhl-1 genes encode homologs of the HIF alpha subunit and VHL. To more fully understand and describe the molecular basis for hypoxia response in this important genetic model system, we compared hypoxia-induced changes in mRNA expression in wild-type, hif-1-deficient, and vhl-1-deficient C. elegans using whole-genome microarrays. These studies identify 110 hypoxia-regulated gene expression changes, 63 of which require hif-1 function. Mutation of vhl-1 abrogates most hif-1-dependent changes in mRNA expression. Genes regulated by C. elegans hif-1 have predicted functions in signal transduction, metabolism, transport, and extra cellular matrix remodeling. We examined the in vivo requirement for 16 HIF-1 target genes and discovered that the phy-2 prolyl 4-hydroxylase alpha subunit is critical for survival in hypoxic conditions. Some HIF-1 target genes negatively regulate formation of stress-resistant dauer larvae. The microarray data presented herein also provide clear evidence for a HIF-1-independent pathway for hypoxia response, and this pathway regulates the expression of multiple heat shock proteins and several transcription factors. Experimental Details: WBPaper00026596:N2_normoxia_vs_N2_hypoxia_Rep1 WBPaper00026596:vhl-1(ok161)_normoxia_vs_vhl-1(ok161)_hypoxia_Rep1 WBPaper00026596:vhl-1(ok161)_normoxia_vs_vhl-1(ok161)_hypoxia_Rep2 WBPaper00026596:hif-1(ia4)_normoxia_vs_hif-1(ia4)_hypoxia_Rep1 WBPaper00026596:vhl-1(ok161)_normoxia_vs_vhl-1(ok161)_hypoxia_Rep3 WBPaper00026596:N2_normoxia_vs_N2_hypoxia_Rep2 WBPaper00026596:N2_normoxia_vs_N2_hypoxia_Rep3 WBPaper00026596:hif-1(ia4)_normoxia_vs_hif-1(ia4)_hypoxia_Rep2 WBPaper00026596:hif-1(ia4)_normoxia_vs_hif-1(ia4)_hypoxia_Rep3. |
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