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| Status |
Public on Jun 30, 2022 |
| Title |
An autoregulatory feedback loop converging on H2AK119ub1 drives synovial sarcoma [CUT&RUN] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The SS18-SSX fusion drives oncogenic transformation in synovial sarcoma by bridging SS18, a member of mSWI/SNF complex, to polycomb repressive complex 1 (PRC1) target genes. Here we show that the SSX C-terminus, via its SSXRD domain, directs SS18-SSX chromatin binding independently of SS18. SSXRD specific targeting is mediated by interaction with H2AK119ub1 and histone MacroH2A with which the fusion overlaps genome wide. Variant Polycomb Repressive Complex 1.1 (PRC1.1) acts as the main depositor of H2AK119ub1 and consequently is required for SS18-SSX occupancy. Importantly, SSX C-terminus not only depends on H2AK119ub1 for localization but also further promotes it and consequently, high H2AK119ub1 levels are acquired during synovial sarcoma development. These results reveal an SS18-SSX/PRC1 autoregulatory feedback-loop that enforces fusion binding and could play a role in a wide-range of cancers and physiological settings where SSX proteins are overexpressed.
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| Overall design |
Chromatin profiles of endogenous SS18-SSX1/2, H2AK119ub1 in human synovial sarcoma cells and HA occupancy in osteosarcoma or synovial sarcoma cells expressing MSCV-HA-eGFP-SS18-PGK-Puro, MSCV-HA-eGFP-SS18-SSX1-PGK-Puro and MSCV-HA-eGFP- SSX-C-PGK-Puro
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| Contributor(s) |
Benabdallah NS, Banito A |
| Citation missing |
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| Submission date |
Jun 12, 2022 |
| Last update date |
May 26, 2023 |
| Contact name |
Nezha Suzanne Benabdallah |
| E-mail(s) |
nsbenabdallah@gmail.com
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| Organization name |
German Cancer Research Center, DKFZ
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| Department |
Functional and Structural Genomics
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| Lab |
Soft-Tissue Sarcoma
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| Street address |
Im Neuenheimer Feld 581 (TP4)
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| City |
Heidelberg |
| ZIP/Postal code |
69120 |
| Country |
Germany |
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| Platforms (2) |
| GPL21697 |
NextSeq 550 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (18)
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| GSM6236007 |
HSSY, PCGF1 knockout, H2Aub1 |
| GSM6236008 |
HSSY, PCGF1 knockout, HA (SS18-SSX1) |
| GSM6236009 |
SYOI, IgG |
| GSM6236010 |
SYOI, Control, H2Aub1 |
| GSM6236011 |
SYOI, Control, SS18-SSX2 |
| GSM6236012 |
SYOI, PCGF1 knockout, H2Aub1 |
| GSM6236013 |
SYOI, PCGF1 knockout, SS18-SSX2 |
| GSM7426492 |
HSSY, IgG, NoDox |
| GSM7426493 |
HSSY, IgG, NoDox, SSX-C, HA |
| GSM7426494 |
HSSY, IgG, Dox, SS18-SSX knockdown, SSX-C, HA |
| GSM7426495 |
KHOS, EV, IgG |
| GSM7426496 |
KHOS, EV, HA |
| GSM7426497 |
KHOS, EV, SS18, HA |
| GSM7426498 |
KHOS, EV, SS18-SSX1, HA |
| GSM7426499 |
KHOS, EV, SSX-C, HA |
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| This SubSeries is part of SuperSeries: |
| GSE205955 |
Aberrant gene activation in synovial sarcoma relies on SSX specificity and increased PRC1.1 stability |
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| Relations |
| BioProject |
PRJNA848408 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE205954_RAW.tar |
1.7 Gb |
(http)(custom) |
TAR (of BIGWIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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