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Series GSE99959 Query DataSets for GSE99959
Status Public on Nov 09, 2017
Title Identification of two types of GGAA microsatellites and their roles in EWS/FLI binding and gene regulation in Ewing sarcoma
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Ewing sarcoma is a bone malignancy of children and young adults, frequently harboring the EWS/FLI t(11;22)(q24;q12) chromosomal translocation. The resulting fusion protein is an aberrant transcription factor that uses highly repetitive GGAA-containing elements (microsatellites) to activate and repress thousands of target genes mediating oncogenesis. However, the mechanisms of EWS/FLI interaction with microsatellites and regulation of target genes expression is not clearly understood. Here, we profile genome-wide protein binding and gene expression. Using a combination of unbiased genome-wide computational and experimental analysis, we define GGAA-microsatellites in a Ewing sarcoma context. Our study identifies two distinct classes of GGAA-microsatellites and demonstrates that EWS/FLI responsiveness is dependent on microsatellite length. At close range (within 5 kb) “promoter-like” microsatellites, EWS/FLI binding and subsequent target genes activation is highly dependent on the number of GGAA-motifs. “Enhancer-like” microsatellites demonstrate a positive correlation with length-dependent EWS/FLI binding, but minimal correlation for activated and none for repressed target genes. Our data suggest that EWS/FLI binds to “promoter-like” and “enhancer-like” microsatellites to mediate activation and repression of target genes through different regulatory mechanisms. Such characterization contributes valuable insight to EWS/FLI transcription factor biology and clarifies the role of GGAA-microsatellites on a global genomic scale. This may provide a unique perspective on the role of non-coding DNA in cancer susceptibility and therapeutic development.
 
Overall design Examination of EWS/FLI binding in A673 cells.
 
Contributor(s) Johnson KM, Taslim C, Saund RS, Lessnick SL
Citation(s) 29091716
Submission date Jun 12, 2017
Last update date May 15, 2019
Contact name Cenny Taslim
E-mail(s) cenny.taslim@nationwidechildrens.org
Organization name Nationwide Children's Hospital
Street address 700 Children's Drive
City Columbus
ZIP/Postal code 43205
Country USA
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (8)
GSM2666470 Input DNA rep1
GSM2666471 Input DNA rep2
GSM2666472 Input DNA rep3
Relations
BioProject PRJNA390192
SRA SRP109046

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE99959_FLI_peaks.xls.gz 683.8 Kb (ftp)(http) XLS
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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