中国科技核心期刊
CN:31-1600/Q
ISSN:1004-0374
2018基因编辑学术研讨会      关于有网站冒充本刊网站的声明
《生命科学》 2017, 29(10): 1040-1045
旁粒组分Nono在小鼠胚胎干细胞中的转录调控机制
胡昊麟,叶宣伽,蓝 斐*
(复旦大学生物医学研究院表观遗传实验室,医学表观遗传与分子代谢国际科技合作基地,上海 200032)
摘 要:旁粒及其组分在肿瘤发生和诸多正常的生物学功能中都扮演了重要的角色,但对于其具体的作用机制仍然缺乏了解。在人和小鼠的胚胎干细胞中,旁粒的关键结构组分长链非编码RNA NEAT1_v2 并不表达,只表达其短变体NEAT1_v1 和3 种旁粒蛋白组分——NONO、SFPQ 和PSPC1,提示这些组分可能具有独立于经典旁粒结构之外的功能。蓝斐课题组依托国家基金委“细胞编程和重编程的表观遗传机制”重大研究计划,在此方向上开展了系统性的研究,并获得了进展:首次发现旁粒蛋白组分Nono 和Erk 相互作用,共同结合在小鼠胚胎干细胞的双价结构域基因(bivalent genes) 的启动子区,并参与Mek/Erk 信号途径调控靶基因的待激活状态;研究还发现,Nono 缺失的mESC 具有更强的自我更新能力,对于胚胎干细胞的体外培养有重要的参考价值。对本领域的最新进展以及复旦大学蓝斐课题组的相关原创性工作进行综述。
 
The transcription regulation mediated by paraspeckle component Nono in mouse embryonic stem cells
HU Hao-Lin, YE Xuan-Jia, LAN Fei*
(Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China)
Abstract: Paraspeckle and its components play important roles in various biological processes, and their malfunction could lead to diseases such as cancer. In human and mouse embryonic stem cells (ESCs), lncRNA NEAT1_v2, the key structural component of paraspeckle stays transcriptionally silent; while its short isoform NEAT1_v1 and three paraspeckle protein components, NONO, SFQP and PSPC1, are well expressed, indicating paraspeckle independent functions. Supported by a NSFC grant focusing on “The Epigenetic Mechanisms of Cell Programming and Reprogramming”, our study uncovered a role of Nono in interacting with Erk and regulating the poised state of RNA polymerase II at bivalent genes in mESCs. Importantly, Nono loss led to an impaired activation of Erk signaling and robust self-renewal of mESC. These findings reveal a previously underappreciated function of paraspeckle components in regulating transcription in chromatin environment and provide alternative approaches to obtain ESCs with robust self-renewing ability. Here, we will debrief the recent advancement in the area and summarize our major findings from the project.
 
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