Gene Set: JUBAN_TARGETS_OF_SPI1_AND_FLI1_DN

Standard name JUBAN_TARGETS_OF_SPI1_AND_FLI1_DN
Systematic name M2394
Brief description Genes down-regulated in 745A cells (erythroleukemia) upon knockdown of FLI1 [GeneID=2313] by RNAi and down-regulation of SPI1 [GeneID=6688] by HMBA [PubChem=3616].
Full description or abstract Spi-1 and Fli-1 are ETS transcription factors recurrently deregulated in mouse erythroleukemia induced by Friend viruses. Since they share the same core DNA binding site, we investigated whether they may contribute to erythroleukemia by common mechanisms. Using inducible knockdown, we demonstrated that Fli-1 contributes to proliferation, survival, and differentiation arrest of erythroleukemic cells harboring an activated fli-1 locus. Similarly, we used inducible Fli-1 knockdown and either hexamethylenebisacetamide (HMBA)- or small interfering RNA-mediated Spi-1 knockdown to investigate their respective contributions in erythroleukemic cells harboring an activated spi-1 locus. In these cells, simple or double knockdown of both Spi-1 and Fli-1 additively contributed to induce proliferation arrest and differentiation. Transcriptome profiling revealed that virtually all transcripts affected by both Fli-1 knockdown and HMBA are affected in an additive manner. Among these additively downregulated transcripts, more than 20% encode proteins involved in ribosome biogenesis, and conserved ETS binding sites are present in their gene promoters. Through chromatin immunoprecipitation, we demonstrated the association of Spi-1 and Fli-1 on these promoters in Friend erythroleukemic cells. These data lead us to propose that the oncogenicity of Spi-1, Fli-1, and possibly other ETS transcription factors may involve their ability to stimulate ribosome biogenesis.
Collection ARCHIVED: Archived Founder gene sets that are referenced by current Hallmarks
      C2_CGP: Archived chemical and genetic perturbations
Source publication Pubmed 19289502   Authors: Juban G,Giraud G,Guyot B,Belin S,Diaz JJ,Starck J,Guillouf C,Moreau-Gachelin F,Morlé F
Exact source Table 3S
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Organism Mus musculus
Contributed by Arthur Liberzon (MSigDB Team)
Source platform UniGene_ID
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Version history 3.1: First introduced

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