EWS-FLI1 target genes recovered from Ewing's sarcoma chromatin View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2005-02-14

AUTHORS

Christine Siligan, Jozef Ban, Radostina Bachmaier, Laura Spahn, Michael Kreppel, Karl-Ludwig Schaefer, Christopher Poremba, Dave N T Aryee, Heinrich Kovar

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. More... »

PAGES

2512-2524

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1208455

DOI

http://dx.doi.org/10.1038/sj.onc.1208455

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1007352020

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15735734


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