Tumor-specific retargeting of an oncogenic transcription factor chimera results in dysregulation of chromatin and transcription

ABSTRACT: 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. Expres

ORGANISM(S): Homo sapiens

SUBMITTER: Ian Davis 

PROVIDER: E-GEOD-31838 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress