Systematic name M6189
Brief description Genes down-regulated in MCF7 cells (breast cancer) after knockdown of both HIF1A and HIF2A [GeneID=3091;2034] by RNAi.
Full description or abstract Studies of gene regulation by oxygen have revealed novel signal pathways that regulate the hypoxia-inducible factor (HIF) transcriptional system through post-translational hydroxylation of specific prolyl and asparaginyl residues in HIF-alpha subunits. These oxygen-sensitive modifications are catalyzed by members of the 2-oxoglutarate (2-OG) dioxygenase family (PHD1, PHD2, PHD3, and FIH-1), raising an important question regarding the extent of involvement of these and other enzymes of the same family in directing the global changes in gene expression that are induced by hypoxia. To address this, we compared patterns of gene expression induced by hypoxia and by a nonspecific 2-OG-dependent dioxygenase inhibitor, dimethyloxalylglycine (DMOG), among a set of 22,000 transcripts, by microarray analysis of MCF7 cells. By using short interfering RNA-based suppression of HIF-alpha subunits, we also compared responses that were dependent on, or independent of, the HIF system. Results revealed striking concordance between patterns of gene expression induced by hypoxia and by DMOG, indicating the central involvement of 2-OG-dependent dioxygenases in oxygen-regulated gene expression. Many of these responses were suppressed by short interfering RNAs directed against HIF-1alpha and HIF-2alpha, with HIF-1alpha suppression manifesting substantially greater effects than HIF-2alpha suppression, supporting the importance of HIF pathways. Nevertheless, the definition of genes regulated by both hypoxia and DMOG, but not HIF, distinguished other pathways most likely involving the action of 2-OG-dependent dioxygenases on non-HIF substrates.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 16565084   Authors: Elvidge GP,Glenny L,Appelhoff RJ,Ratcliffe PJ,Ragoussis J,Gleadle JM
Exact source Tables 3S, 4S: HIF12si fold change < 0 & q-value < 0.01
Related gene sets (show 8 additional gene sets from the source publication)

(show 50 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Arthur Liberzon (Broad Institute)
Source platform HG-U133A
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.0: First introduced

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