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| Status |
Public on Aug 15, 2022 |
| Title |
EWS/FLI mediated reprogramming of 3D chromatin promotes an altered transcriptional state in Ewing sarcoma (4C) |
| Organism |
Homo sapiens |
| Experiment type |
Other
|
| Summary |
Ewing sarcoma is a prototypical fusion transcription factor-associated pediatric cancer that expresses EWS/FLI or highly related fusions. EWS/FLI dysregulates transcription to induce and maintain sarcomagenesis, but the mechanisms utilized are not fully understood. We therefore sought to define the global effects of EWS/FLI on chromatin conformation and transcription in Ewing sarcoma. We found that EWS/FLI (and EWS/ERG) genomic localization is largely conserved across multiple patient-derived Ewing sarcoma cell lines. EWS/FLI binding is primarily associated with compartment activation, establishment of topologically-associated domain (TAD) boundaries, enhancer-promoter looping that involve both intra- and inter-TAD interactions, and gene activation. Importantly, local chromatin features provide the basis for transcriptional heterogeneity in regulation of direct EWS/FLI target genes across different Ewing sarcoma cell lines. These data demonstrate a key role of EWS/FLI in mediating genome-wide changes in chromatin configuration and support the notion that fusion transcription factors serve as master regulators through three-dimensional reprogramming of chromatin.
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| Overall design |
Circular chormatin conformation capture (4C) experiment performed using a GGAA-microsatellite as the viewpoint in A673 EF-Endo, EF-KD and EF-Rescue and in TC71 EF-Endo, EF-KD and EF-Rescue Ewing sarcoma cells.
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| Contributor(s) |
Showpnil IA, Lessnick SL |
| Citation(s) |
36124657 |
| |
| Submission date |
Sep 30, 2021 |
| Last update date |
Oct 26, 2022 |
| Contact name |
Iftekhar Ahmed Showpnil |
| E-mail(s) |
[email protected]
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| Organization name |
Nationwide Children's Hospital
|
| Department |
CCCBD
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| Lab |
Lessnick
|
| Street address |
700 Childrens Drive
|
| City |
Columbus |
| State/province |
OH |
| ZIP/Postal code |
43205 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL22790 |
Illumina MiniSeq (Homo sapiens) |
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| Samples (10)
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| This SubSeries is part of SuperSeries: |
| GSE185132 |
EWS/FLI mediated reprogramming of 3D chromatin promotes an altered transcriptional state in Ewing sarcoma |
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| Relations |
| BioProject |
PRJNA767695 |
| SRA |
SRP339582 |
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