Polycomb repressive complex 2 (PRC2) is central to polycomb repression as it trimethylates lysine 27 on histone H3 (H3K27me3). How PRC2 is recruited to its targets to deposit H3K27me3 remains an open question. Polycomb-like (PCL) proteins, a group of conserved PRC2 accessory proteins, can direct PRC2 to its targets. In this report, we demonstrate that a PCL protein named PHF1 forms phase-separated condensates at H3K27me3 loci that recruit PRC2. Combining cellular observation and biochemical reconstitution, we show that the N-terminal domains of PHF1 cooperatively mediate target recognition, the chromo-like domain recruits PRC2, and the intrinsically disordered region (IDR) drives phase separation. Moreover, we reveal that the condensates compartmentalize PRC2, DNA, and nucleosome arrays by phase separation. Luciferase reporter assays confirm that PHF1 phase separation promotes transcription repression, further supporting a role of the condensates in polycomb repression. Based on our findings, we propose that these condensates create favorable microenvironments at the target loci for PRC2 to function.

中文翻译：

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PHF1 通过相分离分隔 PRC2

Polycomb 抑制复合物 2 (PRC2) 是 Polycomb 抑制的核心，因为它使组蛋白 H3 (H3K27me3) 上的赖氨酸 27 三甲基化。PRC2 如何被招募到其目标来存放 H3K27me3 仍然是一个悬而未决的问题。多梳样 (PCL) 蛋白是一组保守的 PRC2 辅助蛋白，可以引导 PRC2 到达其靶标。在本报告中，我们证明了名为 PHF1 的 PCL 蛋白在 H3K27me3 基因座处形成相分离凝聚物，从而招募 PRC2。结合细胞观察和生化重建，我们发现 PHF1 的 N 端结构域协同介导靶标识别，类染色体结构域招募 PRC2，本质无序区域 (IDR) 驱动相分离。此外，我们揭示了冷凝物通过相分离将 PRC2、DNA 和核小体阵列区分开。荧光素酶报告基因检测证实 PHF1 相分离促进转录抑制，进一步支持缩合物在多梳抑制中的作用。根据我们的研究结果，我们认为这些凝聚物在目标位点上为 PRC2 发挥作用创造了有利的微环境。