Systematic name M16533
Brief description 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.
Full description or abstract 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 15735734   Authors: Siligan C,Ban J,Bachmaier R,Spahn L,Kreppel M,Schaefer KL,Poremba C,Aryee DN,Kovar H
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