INTS11, the catalytic subunit of the Integrator (INT) complex, is crucial for the biogenesis of small nuclear RNAs and enhancer RNAs. However, the role of INTS11 in hematopoietic stem and progenitor cell (HSPC) biology is unknown. Here, we report that INTS11 is required for normal hematopoiesis and hematopoietic-specific genetic deletion of Ints11 leads to cell cycle arrest and impairment of fetal and adult HSPCs. We identified a novel INTS11-interacting protein complex, Polycomb repressive complex 2 (PRC2), that maintains HSPC functions. Loss of INTS11 destabilizes the PRC2 complex, decreases the level of histone H3 lysine 27 trimethylation (H3K27me3), and derepresses PRC2 target genes. Reexpression of INTS11 or PRC2 proteins in Ints11-deficient HSPCs restores the levels of PRC2 and H3K27me3 as well as HSPC functions. Collectively, our data demonstrate that INTS11 is an essential regulator of HSPC homeostasis through the INTS11-PRC2 axis.

中文翻译：

---

INTS11通过促进PRC2功能调节造血

INTS11 是整合子 (INT) 复合物的催化亚基，对小核 RNA 和增强子 RNA 的生物发生至关重要。然而，INTS11 在造血干细胞和祖细胞 (HSPC) 生物学中的作用尚不清楚。在这里，我们报告 INTS11 是正常造血所必需的，并且Ints11的造血特异性基因缺失会导致细胞周期停滞和胎儿和成人 HSPC 受损。我们确定了一种新的 INTS11 相互作用蛋白复合物 Polycomb 抑制复合物 2 (PRC2)，它维持 HSPC 功能。INTS11 的缺失破坏了 PRC2 复合物的稳定性，降低了组蛋白 H3 赖氨酸 27 三甲基化 (H3K27me3) 的水平，并解除了 PRC2 靶基因的抑制。Ints11 中 INTS11 或 PRC2 蛋白的重新表达- 缺乏 HSPCs 可恢复 PRC2 和 H3K27me3 的水平以及 HSPC 功能。总的来说，我们的数据表明，INTS11 是通过 INTS11-PRC2 轴调节 HSPC 稳态的重要调节因子。