STANDARD_NAME	SILIGAN_TARGETS_OF_EWS_FLI1_FUSION_UP
SYSTEMATIC_NAME	M9251
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/SILIGAN_TARGETS_OF_EWS_FLI1_FUSION_UP
NAMESPACE	HUMAN_GENE_SYMBOL
DESCRIPTION_BRIEF	Genes bound by EWSR1-FLT1 [GeneID=2130;2321] fusion and up-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 1B
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	ATP1B1,CDK7,FLJ21613,KIAA1026,KIAA1361,KIAA1432,LIMS1,LIPA,MDH2,NCAM1,NPY,PCLO,RHOBTB3,TCF12,VGF
GENE_SYMBOLS	ATP1B1,CDK7,NAA35,KAZN,TAOK1,RIC1,LIMS1,LIPA,MDH2,NCAM1,NPY,PCLO,RHOBTB3,TCF12,VGF
FOUNDER_NAMES