Oplr16 serves as a novel chromatin factor to control stem cell fate by modulating pluripotency-specific chromosomal looping and TET2-mediated DNA demethylation
Oplr16 serves as a novel chromatin factor to control stem cell fate by modulating pluripotency-specific chromosomal looping and TET2-mediated DNA demethylation
复制标题
Oplr16 作为一种新型染色质因子，通过调节多能性特异性染色体环和 TET2 介导的 DNA 去甲基化来控制干细胞命运
DOI：
10.1093/nar/gkaa097
复制
发表时间：
2020-04-17
影响因子：
14.9
通讯作者：
Hu, Ji-Fan
中科院分区：
文献类型：
--
作者：
Jia, Lin;Wang, Yichen;Hu, Ji-Fan
多能特异性染色质网络的形成是将体细胞重编程为多能状态的关键事件。为了表征这一过程中的调控组分，我们使用“染色质RNA原位逆转录测序”（CRIST-seq）来分析与多能性主基因Oct 4相互作用的RNA组分。使用这种方法，我们鉴定了一种新的核lncRNA 0121，16，其密切参与重编程的起始。Oplr 16不仅与Oct 4启动子相互作用并调节其活性，而且在重编程为多能性期间也被特异性激活。Oplr 16的活性表达是胚胎干细胞多能性最佳维持所必需的。Oplr 16还能够增强成纤维细胞重编程为多能细胞。RNA逆转录相关陷阱测序（RAT-seq）表明，Oplr 16与多个干细胞自我更新相关的靶基因相互作用。值得注意的是，Oplr 16利用其3 '片段募集染色质因子SMC 1来协调多能性特异性染色体内成环。在与Oct 4启动子结合后，Oplr 16募集TET 2以诱导DNA去甲基化并激活成纤维细胞中的Oct 4，从而导致增强的重编程。这些数据表明，Oplr 16可能作为一个关键的染色质因子，通过调节染色质结构和DNA去甲基化来控制干细胞的命运。
Formation of a pluripotency-specific chromatin network is a critical event in reprogramming somatic cells into pluripotent status. To characterize the regulatory components in this process, we used 'chromatin RNA in situ reverse transcription sequencing' (CRIST-seq) to profile RNA components that interact with the pluripotency master gene Oct4. Using this approach, we identified a novel nuclear lncRNA 0121,16 that was closely involved in the initiation of reprogramming. Oplr16 not only interacted with the Oct4 promoter and regulated its activity, but it was also specifically activated during reprogramming to pluripotency. Active expression of Oplr16 was required for optimal maintenance of pluripotency in embryonic stem cells. Oplr16 was also able to enhance reprogramming of fibroblasts into pluripotent cells. RNA reverse transcription-associated trap sequencing (RAT-seq) indicated that Oplr16 interacted with multiple target genes related to stem cell self-renewal. Of note, Oplr16 utilized its 3'-fragment to recruit the chromatin factor SMC1 to orchestrate pluripotency-specific intrachromosomal looping. After binding to the Oct4 promoter, Oplr16 recruited TET2 to induce DNA demethylation and activate Oct4 in fibroblasts, leading to enhanced reprogramming. These data suggest that Oplr16 may act as a pivotal chromatin factor to control stem cell fate by modulating chromatin architecture and DNA demethylation.