Clinical and Translational Research Center of Shanghai First Maternity & Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Science and Technology, Tongji University, Shanghai 200092, China.
Institute of Regenerative Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
J Mol Cell Biol. 2018 Apr 1;10(2):118-129. doi: 10.1093/jmcb/mjx041.
Large-intergenic noncoding RNAs (lincRNAs) cooperate with core transcription factors to coordinate the pluripotency network of embryonic stem cells. The mechanisms by which lincRNAs affect chromatin structure and gene transcription remain mostly unknown. Here, we identified that a lincRNA (linc1614), occupied by pluripotency factors at its promoter, was indispensable for both maintenance and acquisition of pluripotency. Linc1614 served as a specific partner of core factor Sox2 in maintaining pluripotency, primarily by mediating the function of Sox2 in the repression of developmental genes. Moreover, Ezh2, an essential subunit of polycomb repressive complex 2 (PRC2), physically interacted with linc1614 and contributed to lincRNA-mediated transcriptional silencing. Thus, we propose that the interplay of linc1614 with Sox2 implicates this lincRNA as a recruitment platform that mediates transcriptional silencing by guiding the PRC2 complex to the loci of developmental genes.
长链非编码 RNA（lincRNA）与核心转录因子合作，协调胚胎干细胞的多能性网络。lincRNA 影响染色质结构和基因转录的机制在很大程度上尚不清楚。在这里，我们鉴定出一个长链非编码 RNA（linc1614），其启动子被多能性因子占据，对于维持和获得多能性都是必不可少的。Linc1614 作为核心因子 Sox2 在维持多能性中的特异性伙伴，主要通过介导 Sox2 在抑制发育基因中的功能。此外，Ezh2，多梳抑制复合物 2（PRC2）的一个必需亚基，与 linc1614 相互作用，并有助于 lincRNA 介导的转录沉默。因此，我们提出 linc1614 与 Sox2 的相互作用表明该 lincRNA 作为一个募集平台，通过指导 PRC2 复合物到发育基因的位置来介导转录沉默。
