The oncogenic EWS-FLI1 protein binds in vivo GGAA microsatellite sequences with potential transcriptional activation function.

PLoS One 2009 23;4(3):e4932. Epub 2009 Mar 23.

Institut Curie, Paris, France.

The fusion between EWS and ETS family members is a key oncogenic event in Ewing tumors and important EWS-FLI1 target genes have been identified. However, until now, the search for EWS-FLI1 targets has been limited to promoter regions and no genome-wide comprehensive analysis of in vivo EWS-FLI1 binding sites has been undertaken. Using a ChIP-Seq approach to investigate EWS-FLI1-bound DNA sequences in two Ewing cell lines, we show that this chimeric transcription factor preferentially binds two types of sequences including consensus ETS motifs and microsatellite sequences. Most bound sites are found outside promoter regions. Microsatellites containing more than 9 GGAA repeats are very significantly enriched in EWS-FLI1 immunoprecipitates. Moreover, in reporter gene experiments, the transcription activation is highly dependent upon the number of repeats that are included in the construct. Importantly, in vivo EWS-FLI1-bound microsatellites are significantly associated with EWS-FLI1-driven gene activation. Put together, these results point out the likely contribution of microsatellite elements to long-distance transcription regulation and to oncogenesis.

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0004932PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2654724PMC
April 2009
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References

(Supplied by CrossRef)
A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1.
IS Jeon et al.
Oncogene 1995
The FLI-1 and chimeric EWS-FLI-1 oncoproteins display similar DNA binding specificities.
X Mao et al.
J Biol Chem 1994
DNA binding specificities of Spi-1/PU.1 and Spi-B transcription factors and identification of a Spi-1/Spi-B binding site in the c-fes/c-fps promoter.
D Ray-Gallet et al.
Oncogene 1995

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