STANDARD_NAME	ELVIDGE_HIF1A_AND_HIF2A_TARGETS_UP
SYSTEMATIC_NAME	M7062
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/ELVIDGE_HIF1A_AND_HIF2A_TARGETS_UP
NAMESPACE	AFFY_HG_U133
DESCRIPTION_BRIEF	Genes up-regulated in MCF7 cells (breast cancer) after knockdown of both HIF1A and HIF2A [GeneID=3091;2034] by RNAi.
DESCRIPTION_FULL	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.
PMID	16565084
GEOID	GSE3188
AUTHORS	Elvidge GP,Glenny L,Appelhoff RJ,Ratcliffe PJ,Ragoussis J,Gleadle JM
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Tables 3S, 4S: HIF12si fold change > 0 & q-value < 0.01
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	201420_s_at,201516_at,201554_x_at,201700_at,201801_s_at,202070_s_at,202128_at,202433_at,203119_at,203224_at,203372_s_at,204087_s_at,204224_s_at,204233_s_at,205661_s_at,205704_s_at,206976_s_at,207622_s_at,208744_x_at,209083_at,209238_at,209567_at,209666_s_at,209990_s_at,210117_at,211016_x_at,211421_s_at,213427_at,216913_s_at,218196_at,218459_at,218485_s_at,218866_s_at,219090_at,219143_s_at,219384_s_at,219526_at,220011_at,221190_s_at,221536_s_at,221618_s_at,32091_at
GENE_SYMBOLS	WDR77,SRM,GYG1,CCND3,,IDH3A,AREL1,SLC35B1,CCDC86,RFK,SOCS2,SLC5A6,GCH1,CHKA,FLAD1,ATP6V0A2,HSPH1,ABCF2,HSPH1,CORO1A,STX3,RRS1,CHUK,GABBR2,SPAG1,HSPA4,RET,RPP40,RRP12,OSTM1,TOR3A,SLC35C1,POLR3K,SLC24A3,RPP25,ADAT1,RIOX1,AUNIP,RMC1,LSG1,TAF9B,SLC25A44
FOUNDER_NAMES