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| Status |
Public on Oct 27, 2020 |
| Title |
RING1B recruits EWSR1-FLI1 and cooperates in the remodelling of chromatin necessary for Ewing sarcoma tumorigenesis [ChIP-Seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
EWSR1-FLI1 genome reprogramming through remodeling of enhancers is determinant for Ewing sarcoma (ES) tumorigenesis. We describe a non-canonical function of RING1B, a PRC1 subunit highly expressed in primary ES tumors, co-localizing genome wide with EWSR1-FLI1 in active enhancers. While retaining its repressive canonical activity, we find RING1B as necessary for the expression of key EWSR1-FLI1 activated targets like NKX2-2, SOX2 or IGF1 where it mainly exerts a role in promoting oncogene recruitment to enhancers. Knockdown of RING1B is sufficient to impair growth of tumor xenografts and expression of EWSR1-FLI1 induced neomorphic enhancers in vivo. Restoration of RING1B ubiquitin ligase activity by the AURKB inhibitor AZD1152 decreases expression of RING1B/EWSR1-FLI1 common targets. Overall, our findings demonstrate RING1B as a critical modulator of EWSR1-FLI1 induced chromatin remodeling.
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| Overall design |
ChIPseq for RING1B (2 replicates), INPUT for RING1B (2 replicates), H2Aub1 (2 replicates) and INPUT for H2Aub1 (2 replicates). ChIPseq for BMI1, CBX7, EWSR1-FLI1 and INPUT (1 replicate). ChIPseq for RING1B, EWSR1-FLI1 and INPUT (shCTRL and shRING1B conditions).
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| |
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| Contributor(s) |
Sanchez S, Blanco E |
| Citation(s) |
33097530 |
| |
| Submission date |
May 15, 2019 |
| Last update date |
Oct 27, 2020 |
| Contact name |
Enrique Blanco |
| E-mail(s) |
enrique.blanco@crg.eu
|
| Phone |
+34 93 316 01 00
|
| Organization name |
Center for Genomic Regulation (CRG)
|
| Department |
Gene Regulation, Stem Cells and Cancer
|
| Lab |
Epigenetic Events in Cancer (L. Di Croce's lab)
|
| Street address |
Dr. Aiguader 88
|
| City |
Barcelona |
| ZIP/Postal code |
08003 |
| Country |
Spain |
| |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (18)
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| This SubSeries is part of SuperSeries: |
| GSE133427 |
RING1B recruits EWSR1-FLI1 and cooperates in the remodelling of chromatin necessary for Ewing sarcoma tumorigenesis |
|
| Relations |
| BioProject |
PRJNA543121 |
| SRA |
SRP198531 |
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