Many chromatin-binding proteins and protein complexes that regulate transcription also bind RNA. One of these, Polycomb repressive complex 2 (PRC2), deposits the H3K27me3 mark of facultative heterochromatin and is required for stem cell differentiation. PRC2 binds RNAs broadly in vivo and in vitro. Yet, the biological importance of this RNA binding remains unsettled. Here, we tackle this question in human induced pluripotent stem cells by using multiple complementary approaches. Perturbation of RNA–PRC2 interaction by RNase A, by a chemical inhibitor of transcription or by an RNA-binding-defective mutant all disrupted PRC2 chromatin occupancy and localization genome wide. The physiological relevance of PRC2–RNA interactions is further underscored by a cardiomyocyte differentiation defect upon genetic disruption. We conclude that PRC2 requires RNA binding for chromatin localization in human pluripotent stem cells and in turn for defining cellular state.

许多调节转录的染色质结合蛋白和蛋白复合物也结合 RNA。其中之一，Polycomb 抑制复合物 2 (PRC2)，沉积兼性异染色质的 H3K27me3 标记，是干细胞分化所必需的。PRC2 在体内和体外广泛结合 RNA。然而，这种 RNA 结合的生物学重要性仍然悬而未决。在这里，我们通过使用多种互补方法在人类诱导多能干细胞中解决这个问题。RNase A、化学转录抑制剂或 RNA 结合缺陷突变体对 RNA-PRC2 相互作用的干扰都会破坏 PRC2 染色质占据和全基因组定位。遗传破坏后心肌细胞分化缺陷进一步强调了 PRC2-RNA 相互作用的生理相关性。我们得出的结论是，PRC2 需要 RNA 结合来实现人类多能干细胞中染色质的定位，进而定义细胞状态。