Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA145117 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR342293.fastq.gz | Fastqsanger.gz | |||
| SRR342294.fastq.gz | Fastqsanger.gz | |||
| SRR342295.fastq.gz | Fastqsanger.gz | |||
| SRR342296.fastq.gz | Fastqsanger.gz | |||
| SRR342297.fastq.gz | Fastqsanger.gz |
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2011-11-09 | E-GEOD-31838 | biostudies-arrayexpress
Project description: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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