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| Status |
Public on Nov 09, 2011 |
| Title |
Tumor-specific retargeting of an oncogenic transcription factor chimera results in dysregulation of chromatin and transcription |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Using EWS-FLI and its parental transcription factor, FLI1, we created a unique experimental system to address questions regarding the genomic mechanisms by which chimeric transcription factors cause cancer. We found that in tumor cells, EWS-FLI targets regions of the genome distinct from FLI1, despite identical DNA-binding domains. In primary endothelial cells, however, EWS-FLI and FLI1 demonstrate similar targeting. To understand this mistargeting, we examined chromatin organization. Regions targeted by EWS-FLI are normally repressed and nucleosomal in primary endothelial cells. In tumor cells, however, bound regions are nucleosome-depleted and harbor the chromatin signature of enhancers. We next demonstrated that through chimerism, EWS-FLI acquired the ability to alter chromatin. Expression of EWS-FLI results in nucleosome depletion at targeted sites, whereas silencing of EWS-FLI in tumor cells restored nucleosome occupancy. Thus, the EWS-FLI chimera acquired chromatin-altering activity, leading to mistargeting, chromatin disruption, and ultimately transcriptional dysregulation.
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| Overall design |
Examination of two transcription factors in two different cell types, as well as three histone methylation marks and FAIRE
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| Contributor(s) |
Patel MK, Simon JM, Lieb JD, Davis IJ |
| Citation(s) |
22086061 |
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| Submission date |
Sep 01, 2011 |
| Last update date |
May 12, 2023 |
| Contact name |
Ian Jonathan Davis |
| E-mail(s) |
ian_davis@med.unc.edu
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| Phone |
919-966-5360
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| Organization name |
University of North Carolina
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| Department |
Genetics, Pediatrics
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| Street address |
450 West Drive
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| City |
Chapel Hill |
| State/province |
NC |
| ZIP/Postal code |
27599 |
| Country |
USA |
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| Platforms (2) |
| GPL5188 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [probe set (exon) version] |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
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| Samples (32)
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| Relations |
| SRA |
SRP008121 |
| BioProject |
PRJNA145117 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE31838_RAW.tar |
5.0 Gb |
(http)(custom) |
TAR (of BED, CEL) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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