| EWS-FLI1 target genes recovered from Ewing's sarcoma chromatin. | |
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MedLine Citation:
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PMID: 15735734 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Christine Siligan; Jozef Ban; Radostina Bachmaier; Laura Spahn; Michael Kreppel; Karl-Ludwig Schaefer; Christopher Poremba; Dave N T Aryee; Heinrich Kovar |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Oncogene Volume: 24 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 2005 Apr |
Date Detail:
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Created Date: 2005-04-07 Completed Date: 2005-05-16 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 2512-24 Citation Subset: IM |
Affiliation:
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Children's Cancer Research Institute (CCRI), St Anna Kinderspital, Kinderspitalgasse 6, Vienna A1090, Austria. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Bone Neoplasms
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genetics* Chromatin / genetics* DNA, Neoplasm / analysis DNA-Binding Proteins / genetics* Gene Expression Profiling Humans Immunoprecipitation Oligonucleotide Array Sequence Analysis Protein Tyrosine Phosphatases / genetics, pharmacology* Proto-Oncogene Protein c-fli-1 RNA-Binding Protein EWS / genetics* Sarcoma, Ewing's / genetics* Trans-Activators / genetics* |
| Chemical | |
Reg. No./Substance:
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0/Chromatin; 0/DNA, Neoplasm; 0/DNA-Binding Proteins; 0/FLI1 protein, human; 0/Proto-Oncogene Protein c-fli-1; 0/RNA-Binding Protein EWS; 0/Trans-Activators; EC 3.1.3.48/Protein Tyrosine Phosphatases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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