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EWS-FLI1 target genes recovered from Ewing's sarcoma chromatin.
- Source :
- Oncogene; 4/7/2005, Vol. 24 Issue 15, p2512-2524, 13p
- Publication Year :
- 2005
-
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.Oncogene (2005) 24, 2512-2524. doi:10.1038/sj.onc.1208455 Published online 14 February 2005 [ABSTRACT FROM AUTHOR]
- Subjects :
- EWING'S sarcoma
OSTEOSARCOMA
CHROMATIN
GENETICS
GENES
INTRONS
PROTEINS
Subjects
Details
- Language :
- English
- ISSN :
- 09509232
- Volume :
- 24
- Issue :
- 15
- Database :
- Complementary Index
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 16668905
- Full Text :
- https://doi.org/10.1038/sj.onc.1208455