Gene Set: GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_DN

Standard name GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_DN
Systematic name M1318
Brief description Genes down-regulated in SEND cells (skin endothelium) at hypoxia after knockdown of ELK3 [GeneID=2004] and HIF1A [GeneID=3091] by RNAi.
Full description or abstract The ternary complex factor Net/Elk3 is downregulated in hypoxia and participates in the induction by hypoxia of several genes, including c-fos, vascular endothelial growth factor and egr-1. However, the global role of Net in hypoxia remains to be elucidated. We have identified, in a large-scale analysis of RNA expression using microarrays, more than 370 genes that are regulated by Net in hypoxia. In order to gain insights into the role of Net in hypoxia, we have analysed in parallel the genes regulated by HIF-1alpha, the classical factor involved in the response to hypoxia. We identified about 190 genes that are regulated by HIF-1alpha in hypoxia. Surprisingly, when we compare the genes induced by hypoxia that require either Net or HIF-1alpha, the majority are the same (75%), suggesting that the functions of both factors are closely linked. Interestingly, in hypoxia, Net regulates the expression of several genes known to control HIF-1alpha stability, including PHD2, PHD3 and Siah2, suggesting that Net regulates the stability of HIF-1alpha. We found that inhibition of Net by RNAi leads to decreased HIF-1alpha expression at the protein level in hypoxia. These results indicate that Net participates in the transcriptional response to hypoxia by regulation of HIF-1alpha protein stability.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17704799   Authors: Gross C,Dubois-Pot H,Wasylyk B
Exact source Table 7S
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Organism Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform MOUSE_SEQ_ACCESSION
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Version history 3.1: First introduced

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