TY  - JOUR
AU  - Benabdallah, Nezha Suzanne
AU  - Dalal, Vineet
AU  - Scott, R Wilder
AU  - Marcous, Fady
AU  - Sotiriou, Afroditi
AU  - Kommoss, Felix Karl-Friedrich
AU  - Pejkovska, Anastasija
AU  - Gaspar, Ludmila
AU  - Wagner, Lena
AU  - Sánchez-Rivera, Francisco J
AU  - Ta, Monica
AU  - Thornton, Shelby
AU  - Nielsen, Torsten O
AU  - Underhill, T Michael
AU  - Banito, Ana
TI  - Aberrant gene activation in synovial sarcoma relies on SSX specificity and increased PRC1.1 stability.
JO  - Nature structural & molecular biology
VL  - 30
IS  - 11
SN  - 1545-9993
CY  - London [u.a.]
PB  - Nature Publishing Group
M1  - DKFZ-2023-01910
SP  - 1640-1652
PY  - 2023
N1  - #EA:B380#LA:B380# / 2023 Nov;30(11):1640-1652
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:37735617
DO  - DOI:10.1038/s41594-023-01096-3
UR  - https://inrepo02.dkfz.de/record/282958
ER  -