STANDARD_NAME SILIGAN_TARGETS_OF_EWS_FLI1_FUSION_DN SYSTEMATIC_NAME M16533 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/SILIGAN_TARGETS_OF_EWS_FLI1_FUSION_DN NAMESPACE HUMAN_GENE_SYMBOL DESCRIPTION_BRIEF Genes bound by EWSR1-FLT1 [GeneID=2130;2321] fusion and down-regulated in STA-ET-7.2 cells (Ewing's sarcoma) after knockdown of EWSR1-FLT1 by RNAi. DESCRIPTION_FULL In all, 85% of Ewing's sarcoma family tumors (ESFT), a neoplasm of unknown histogenesis, express EWS-FLI1 transcription factor gene fusions. To characterize direct target genes avoiding artificial model systems, we cloned genomic DNA from ESFT chromatin precipitating with EWS-FLI1. We now present a comprehensive list of 99 putative transcription factor targets identified, for the first time, by a hypothesis-free approach based on physical interaction. Gene-derived chromatin fragments co-precipitating with EWS-FLI1 were nonrandomly distributed over the human genome and localized predominantly to the upstream region and the first two introns of the genes. At least 20% of putative direct EWS-FLI1 targets were neural genes. One-third of genes recovered showed a significant ESFT-specific expression pattern and were found to be altered upon RNAi-mediated knockdown of EWS-FLI1. Among them, MK-STYX, encoding a MAP kinase phosphatase-like protein, was consistently expressed in ESFT. EWS-FLI1 was found to drive MK-STYX expression by binding to a single ETS binding motif within the first gene intron. MK-STYX serves as precedence for successful recovery of direct EWS-FLI1 targets from the authentic ESFT cellular context, the most relevant system to study oncogenic mechanisms for the discovery of new therapeutic targets in this disease. PMID 15735734 GEOID AUTHORS Siligan C,Ban J,Bachmaier R,Spahn L,Kreppel M,Schaefer KL,Poremba C,Aryee DN,Kovar H CONTRIBUTOR Arthur Liberzon CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 1A FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS ACCN1,ASNS,CDC14B,CLASP2,CNTNAP2,DLG2,GTF2E2,IDH3B,LRBA,MK-STYX,NOL5A,PCCA,PFTK1,POT1,RFC1,SLC2A5,SSR3,TBL1X GENE_SYMBOLS ASIC2,ASNS,CDC14B,CLASP2,CNTNAP2,DLG2,GTF2E2,IDH3B,LRBA,STYXL1,NOP56,PCCA,CDK14,POT1,RFC1,SLC2A5,SSR3,TBL1X FOUNDER_NAMES