Hou Weibo, Zong Ming, Zhao Qi, Yang Xu, Zhang Jiaming, Liu Shuanghui, Li Xuanwen, Chen Lijun, Tang Chun, Wang Xinyu, Dong Zhixiong, Gao Meiling, Su Jianzhong, Kong Qingran
Oujiang Laboratory, Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
College of Life Science, Northeast Agricultural University, Harbin, Heilongjiang, China.
iScience. 2023 Jul 26;26(8):107469. doi: 10.1016/j.isci.2023.107469. eCollection 2023 Aug 18.
Long non-coding RNAs (lncRNAs) have been implicated in diverse biological processes. However, the functional mechanisms have not yet been fully explored. Characterizing the interactions of lncRNAs with chromatin is central to determining their functions but, due to precise and efficient approaches lacking, our understanding of their functional mechanisms has progressed slowly. In this study, we demonstrate that a nuclear lncRNA linc1393 maintains mouse ESC pluripotency by recruiting SET1A near its binding sites, to establish H3K4me3 status and activate the expression of specific pluripotency-related genes. Moreover, we characterized the principles of lncRNA-chromatin interaction and transcriptional regulation. Accordingly, we developed a computational framework based on the XGBoost model, LncTargeter, to predict the targets of a given lncRNA, and validated its reliability in various cellular contexts. Together, these findings elucidate the roles and mechanisms of lncRNA on pluripotency maintenance, and provide a promising tool for predicting the regulatory networks of lncRNAs.
长链非编码RNA（lncRNA）参与了多种生物学过程。然而，其功能机制尚未得到充分探索。表征lncRNA与染色质的相互作用对于确定其功能至关重要，但由于缺乏精确有效的方法，我们对其功能机制的理解进展缓慢。在本研究中，我们证明核lncRNA linc1393通过在其结合位点附近招募SET1A来维持小鼠胚胎干细胞的多能性，以建立H3K4me3状态并激活特定多能性相关基因的表达。此外，我们表征了lncRNA-染色质相互作用和转录调控的原理。因此，我们基于XGBoost模型开发了一个计算框架LncTargeter，以预测给定lncRNA的靶标，并在各种细胞环境中验证了其可靠性。这些发现共同阐明了lncRNA在多能性维持中的作用和机制，并为预测lncRNA的调控网络提供了一个有前景的工具。
