Nuclear condensates have been shown to regulate cell fate control, but its role in oncogenic transformation remains largely unknown. Here we show acquisition of oncogenic potential by nuclear condensate remodeling. The proto-oncogene SS18 and its oncogenic fusion SS18-SSX1 can both form condensates, but with drastically different properties and impact on 3D genome architecture. The oncogenic condensates, not wild type ones, readily exclude HDAC1 and 2 complexes, thus, allowing aberrant accumulation of H3K27ac on chromatin loci, leading to oncogenic expression of key target genes. These results provide the first case for condensate remodeling as a transforming event to generate oncogene and such condensates can be targeted for therapy. One sentence summary: Expulsion of HDACs complexes leads to oncogenic transformation.

中文翻译：

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致癌核凝聚物排除 HDAC1/2 复合物

核凝聚物已被证明可以调节细胞命运控制，但其在致癌转化中的作用仍然很大程度上未知。在这里，我们展示了通过核凝聚重塑获得致癌潜力。原癌基因 SS18 及其致癌融合体 SS18-SSX1 都可以形成凝聚物，但具有截然不同的特性和对 3D 基因组结构的影响。致癌浓缩物（而非野生型浓缩物）很容易排除 HDAC1 和 2 复合物，因此允许 H3K27ac 在染色质位点上异常积累，导致关键靶基因的致癌表达。这些结果提供了第一个将冷凝重塑作为产生癌基因的转化事件的案例，并且这种冷凝可以作为治疗的目标。一句话总结：HDAC复合物的排出导致致癌转化。