小柯机器人

PRC2在人类多能干细胞中发挥功能依赖与RNA结合
2020-07-10 11:46

2020年7月6日,《自然—遗传学》杂志在线发表了美国科罗拉多大学Thomas R. Cech、John L. Rinn等研究人员的合作成果。他们的研究表明,RNA对于PRC2在人类多能干细胞中结合染色质以及发挥其功能至关重要。

研究人员表示,许多染色质结合蛋白和调节转录的蛋白复合物也结合RNA。其中之一,Polycomb抑制复合物2(PRC2)负责修饰兼性异染色质的H3K27me3标志,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结合的生物学意义尚未确定。
 
研究人员通过使用多种互补方法解决了人类诱导的多能干细胞中的这个问题。RNase A处理、转录化学抑制剂或RNA结合缺陷型突变体对RNA-PRC2相互作用的扰动都破坏了PRC2染色质的占据以及整个基因组范围的定位。基因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。研究人员认为,PRC2需要RNA结合才能在人类多能干细胞中定位染色质,进而定义细胞状态。
 
附:英文原文

Title: RNA is essential for PRC2 chromatin occupancy and function in human pluripotent stem cells

Author: Yicheng Long, Taeyoung Hwang, Anne R. Gooding, Karen J. Goodrich, John L. Rinn, Thomas R. Cech

Issue&Volume: 2020-07-06

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.

DOI: 10.1038/s41588-020-0662-x

Source: https://www.nature.com/articles/s41588-020-0662-x

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

分享到:

0