Mutations and deletions of polycomb repressive complex (PRC) components are increasingly recognized to affect tumor biology in a range of cancers. However, little is known about how genetic alterations of PRC-interacting molecules such as the core binding factor (CBF) complex influence polycomb activity. We report that the acute myeloid leukemia (AML)-associated CBFβ-SMMHC fusion oncoprotein physically interacts with the PRC1 complex and that these factors co-localize across the AML genome in an apparently PRC2-independent manner. Depletion of CBFβ-SMMHC caused substantial increases in genome-wide PRC1 binding and marked changes in the association between PRC1 and the CBF DNA-binding subunit RUNX1. PRC1 was more likely to be associated with actively transcribed genes in CBFβ-SMMHC-expressing cells. CBFβ-SMMHC depletion had heterogeneous effects on gene expression, including significant reductions in transcription of ribosomal loci occupied by PRC1. Our results provide evidence that CBFβ-SMMHC markedly and diversely affects polycomb recruitment and transcriptional regulation across the AML genome.

中文翻译：

---

CBFβ-SMMHC影响急性髓性白血病的全基因组多梳抑制复合物1活性。

越来越多地认识到多梳抑制复合物（PRC）组件的突变和缺失会影响多种癌症中的肿瘤生物学。然而，关于诸如核心结合因子（CBF）复合物之类的PRC交互分子的遗传改变如何影响多梳活性的消息鲜为人知。我们报告说，急性髓细胞性白血病（AML）相关的CBFβ-SMMHC融合癌蛋白与PRC1复合体发生物理相互作用，并且这些因子以明显独立于PRC2的方式共定位于整个AML基因组。CBFβ-SMMHC的耗竭引起全基因组PRC1结合的显着增加，并且PRC1和CBF DNA结合亚基RUNX1之间的关联发生了显着变化。PRC1更有可能与表达CBFβ-SMMHC的细胞中的主动转录基因相关。CBFβ-SMMHC耗竭对基因表达具有异质性影响，包括显着减少PRC1占据的核糖体基因座的转录。我们的结果提供了证据，即CBFβ-SMMHC显着不同地影响整个AML基因组中的多梳募募和转录调控。