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| Home > Publications database > Aberrant gene activation in synovial sarcoma relies on SSX specificity and increased PRC1.1 stability. > print |
| Home > Publications database > Aberrant gene activation in synovial sarcoma relies on SSX specificity and increased PRC1.1 stability. > print |
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| 100 | 1 | _ | |a Benabdallah, Nezha Suzanne |0 P:(DE-He78)b74d7041806f139a13c57351adf92984 |b 0 |e First author |u dkfz |
| 245 | _ | _ | |a Aberrant gene activation in synovial sarcoma relies on SSX specificity and increased PRC1.1 stability. |
| 260 | _ | _ | |a London [u.a.] |c 2023 |b Nature Publishing Group |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 500 | _ | _ | |a #EA:B380#LA:B380# / 2023 Nov;30(11):1640-1652 |
| 520 | _ | _ | |a The SS18-SSX fusion drives oncogenic transformation in synovial sarcoma by bridging SS18, a member of the mSWI/SNF (BAF) complex, to Polycomb repressive complex 1 (PRC1) target genes. Here we show that the ability of SS18-SSX to occupy H2AK119ub1-rich regions is an intrinsic property of its SSX C terminus, which can be exploited by fusion to transcriptional regulators beyond SS18. Accordingly, SS18-SSX recruitment occurs in a manner that is independent of the core components and catalytic activity of BAF. Alternative SSX fusions are also recruited to H2AK119ub1-rich chromatin and reproduce the expression signatures of SS18-SSX by engaging with transcriptional activators. Variant Polycomb repressive complex 1.1 (PRC1.1) acts as the main depositor of H2AK119ub1 and is therefore required for SS18-SSX occupancy. Importantly, the SSX C terminus not only depends on H2AK119ub1 for localization, but also further increases it by promoting PRC1.1 complex stability. Consequently, high H2AK119ub1 levels are a feature of murine and human synovial sarcomas. These results uncover a critical role for SSX-C in mediating gene deregulation in synovial sarcoma by providing specificity to chromatin and further enabling oncofusion binding by enhancing PRC1.1 stability and H2AK119ub1 deposition. |
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| 700 | 1 | _ | |a Sánchez-Rivera, Francisco J |0 0000-0002-8466-8563 |b 9 |
| 700 | 1 | _ | |a Ta, Monica |b 10 |
| 700 | 1 | _ | |a Thornton, Shelby |b 11 |
| 700 | 1 | _ | |a Nielsen, Torsten O |0 0000-0003-3769-2517 |b 12 |
| 700 | 1 | _ | |a Underhill, T Michael |0 0000-0003-3048-9102 |b 13 |
| 700 | 1 | _ | |a Banito, Ana |0 P:(DE-He78)990de6ec6c2f0a40b17ed75162ca19e8 |b 14 |e Last author |u dkfz |
| 773 | _ | _ | |a 10.1038/s41594-023-01096-3 |0 PERI:(DE-600)2131437-8 |n 11 |p 1640-1652 |t Nature structural & molecular biology |v 30 |y 2023 |x 1545-9993 |
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