Journal Article

DKFZ-2023-01910

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Aberrant gene activation in synovial sarcoma relies on SSX specificity and increased PRC1.1 stability.

Benabdallah, N. S. (First author)DKFZ* ; Dalal, V.DKFZ* ; Scott, R. W. ; Marcous, F.DKFZ* ; Sotiriou, A.DKFZ* ; Kommoss, F. K.DKFZ* ; Pejkovska, A.DKFZ* ; Gaspar, L.DKFZ* ; Wagner, L.DKFZ* ; Sánchez-Rivera, F. J. ; Ta, M. ; Thornton, S. ; Nielsen, T. O. ; Underhill, T. M. ; Banito, A. (Last author)DKFZ*

2023
Nature Publishing Group London [u.a.]

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Please use a persistent id in citations: doi:10.1038/s41594-023-01096-3

Abstract: 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.

Note: #EA:B380#LA:B380# / 2023 Nov;30(11):1640-1652

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Contributing Institute(s):

1. NWG Weichteilsarkome (B380)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 15 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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