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@ARTICLE{Benabdallah:282958,
author = {N. S. Benabdallah$^*$ and V. Dalal$^*$ and R. W. Scott and
F. Marcous$^*$ and A. Sotiriou$^*$ and F. K. Kommoss$^*$ and
A. Pejkovska$^*$ and L. Gaspar$^*$ and L. Wagner$^*$ and F.
J. Sánchez-Rivera and M. Ta and S. Thornton and T. O.
Nielsen and T. M. Underhill and A. Banito$^*$},
title = {{A}berrant gene activation in synovial sarcoma relies on
{SSX} specificity and increased {PRC}1.1 stability.},
journal = {Nature structural $\&$ molecular biology},
volume = {30},
number = {11},
issn = {1545-9993},
address = {London [u.a.]},
publisher = {Nature Publishing Group},
reportid = {DKFZ-2023-01910},
pages = {1640-1652},
year = {2023},
note = {#EA:B380#LA:B380# / 2023 Nov;30(11):1640-1652},
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.},
cin = {B380},
ddc = {570},
cid = {I:(DE-He78)B380-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37735617},
doi = {10.1038/s41594-023-01096-3},
url = {https://inrepo02.dkfz.de/record/282958},
}