Synovial sarcoma is an aggressive cancer invariably associated with a chromosomal translocation involving genes encoding the SWI-SNF complex component SS18 and an SSX (SSX1 or SSX2) transcriptional repressor. Using functional genomics, we identify KDM2B, a histone demethylase and component of a non-canonical polycomb repressive complex 1 (PRC1.1), as selectively required for sustaining synovial sarcoma cell transformation. SS18-SSX1 physically interacts with PRC1.1 and co-associates with SWI/SNF and KDM2B complexes on unmethylated CpG islands. Via KDM2B, SS18-SSX1 binds and aberrantly activates expression of developmentally regulated genes otherwise targets of polycomb-mediated repression, which is restored upon KDM2B depletion, leading to irreversible mesenchymal differentiation. Thus, SS18-SSX1 deregulates developmental programs to drive transformation by hijacking a transcriptional repressive complex to aberrantly activate gene expression.

中文翻译：

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SS18-SSX癌蛋白劫持了KDM2B-PRC1.1以驱动滑膜肉瘤。

滑膜肉瘤是一种侵袭性癌症，总是与染色体易位相关，涉及编码SWI-SNF复杂成分SS18和SSX（SSX1或SSX2）转录阻遏物的基因。使用功能基因组学，我们确定KDM2B，组蛋白脱甲基酶和非规范化的多梳抑制复合物1（PRC1.1）的组成部分，以选择性维持滑膜肉瘤细胞转化。SS18-SSX1与PRC1.1进行物理交互，并与未甲基化的CpG岛上的SWI / SNF和KDM2B配合物共缔合。通过KDM2B，SS18-SSX1结合并异常激活发育调控基因的表达，否则其成为多梳介导的阻遏的靶标，该靶标在KDM2B耗尽后得以恢复，导致不可逆的间充质分化。因此，