RNA 对于 PRC2 染色质在人多能干细胞中的占据和功能是必需的。
RNA is essential for PRC2 chromatin occupancy and function in human pluripotent stem cells.
机构信息
Department of Biochemistry and BioFrontiers Institute, University of Colorado, Boulder, CO, USA.
Howard Hughes Medical Institute, University of Colorado, Boulder, CO, USA.
出版信息
Nat Genet. 2020 Sep;52(9):931-938. doi: 10.1038/s41588-020-0662-x. Epub 2020 Jul 6.
Abstract
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.
摘要
许多调节转录的染色质结合蛋白和蛋白复合物也与 RNA 结合。其中之一是多梳抑制复合物 2（PRC2），它沉积了组成性异染色质的 H3K27me3 标记，并且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未确定。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了这个问题。用 RNase A、转录化学抑制剂或 RNA 结合缺陷突变体来干扰 RNA-PRC2 相互作用，都会破坏 PRC2 染色质在全基因组上的占据和定位。PRC2-RNA 相互作用的生理相关性进一步通过基因敲除导致的心肌细胞分化缺陷得到强调。我们的结论是，PRC2 在人类多能干细胞中需要 RNA 结合才能进行染色质定位，进而确定细胞状态。
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