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000282958 245__ $$aAberrant gene activation in synovial sarcoma relies on SSX specificity and increased PRC1.1 stability.
000282958 260__ $$aLondon [u.a.]$$bNature Publishing Group$$c2023
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000282958 500__ $$a#EA:B380#LA:B380# / 2023 Nov;30(11):1640-1652
000282958 520__ $$aThe 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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000282958 7001_ $$00000-0001-7608-7489$$aScott, R Wilder$$b2
000282958 7001_ $$0P:(DE-He78)046fa741843a759cd2e7f298ca067351$$aMarcous, Fady$$b3$$udkfz
000282958 7001_ $$0P:(DE-He78)22a75eda770719cdf28614de8de0d711$$aSotiriou, Afroditi$$b4$$udkfz
000282958 7001_ $$0P:(DE-He78)0da1ad006d075546f49fd10e062da5d2$$aKommoss, Felix Karl-Friedrich$$b5$$udkfz
000282958 7001_ $$0P:(DE-He78)5f1c822f3bde55a84c31681d50ce1dd5$$aPejkovska, Anastasija$$b6$$udkfz
000282958 7001_ $$0P:(DE-He78)d9bfaa5de532eb676a5a8195001de350$$aGaspar, Ludmila$$b7
000282958 7001_ $$0P:(DE-He78)dafca537433ee26708b96d89aba38d29$$aWagner, Lena$$b8
000282958 7001_ $$00000-0002-8466-8563$$aSánchez-Rivera, Francisco J$$b9
000282958 7001_ $$aTa, Monica$$b10
000282958 7001_ $$aThornton, Shelby$$b11
000282958 7001_ $$00000-0003-3769-2517$$aNielsen, Torsten O$$b12
000282958 7001_ $$00000-0003-3048-9102$$aUnderhill, T Michael$$b13
000282958 7001_ $$0P:(DE-He78)990de6ec6c2f0a40b17ed75162ca19e8$$aBanito, Ana$$b14$$eLast author$$udkfz
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