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LincRNA-1614 coordinates Sox2/PRC2-mediated repression of developmental genes in pluripotency maintenance

Journal of Molecular Cell Biology 2018年第2期10卷 118-129页

作者： Xudong Guo Zikang Wang Chenqi Lu Wujun Hong Guiying Wang Yanxin Xu Zhongmin Liu Jiuhong Kang 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 Laboratory of Population and Quantitative Genetics institute of Biostatistics School of Life Sciences Fudan University Shanghai 200433 China

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 UncRNA （linc1614）, occupied by pluripotency factors at its promoter, was indispensable for both maintenance and acquisition of pluripotency. Linc1614 sewed 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.

关键词： lincRNA Sox2 pluripotency maintenance PRC2 reprogramming

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LincRNA1230 inhibits the differentiation of mouse ES cells towards neural progenitors

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Science China(Life Sciences) 2016年第5期59卷 443-454页

作者： Chenxin Wang Guoping Li Yukang Wu Jiajie Xi Jiuhong Kang Clinical and Translational Research Center of Shanghai First Maternity and 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

In vitro, mouse embryonic stem （ES） cells can differentiate into many somatic cell types, including neurons and glial cells. When cultured in serum-free medium, ES cells convert spontaneously and efficiently to a neural fate. Previous studies have shown that the neural conversion of mouse ES cells includes both the participation of neural-specific transcription factors and the regulation of epigenetic modifications. However, the intracellular mechanism underlying this intrinsic transition still re- mains to be further elucidated. Herein, we describe a long intergenic non-coding RNA, LincRNA1230, which participates in the regulation of the neural lineage specification of mouse ES cells. The ectopic forced expression of LincRNAI230 dramatically inhibited mouse ES cells from adopting a neural cell fate, while LincRNA1230 knockdown promoted the conversion of mouse ES cells towards neural progenitors. Mechanistic studies have shown that LincRNA1230 inhibits the activation of early neural genes, such as Pax6 and Soxl, through the modulation of bivalent modifications （tri-methylation of histone3 lysine4 and his- tone3 lysine27） at the promoters of these genes. The interaction of LincRNA1230 with Wdr5 blocked the localization of Wdr5 at the promoters of early neural genes, thereby inhibiting the enrichment of H3K4me3 modifications at these loci. Collectively, these findings revealed a crucial role for LincRNA1230 in the regulation of the neural differentiation of mouse ES cells.

关键词： mouse ES cells neural differentiation long non-coding RNA (IncRNA) bivalent modification Wdr5

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LincRNA1230抑制小鼠胚胎干细胞向神经前体细胞分化

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中国科学：生命科学 2016年第6期46卷 723-734页

作者：王晨鑫李国平武玉康奚佳捷康九红同济大学附属第一妇婴保健院临床与转化研究中心上海200092 同济大学生命科学与技术学院上海市信号与疾病研究重点实验室上海200092 脑科学协同创新中心上海200092

胚胎干细胞是一类具有多向分化潜能的细胞.胚胎干细胞可以模拟体内发育过程,在无外界信号分子刺激的情况下,自发向神经前体细胞分化.有研究表明,这一体外发育过程受神经分化相关转录因子和表观遗传修饰的共同调控,然而该过程中的分子机... 详细信息

胚胎干细胞是一类具有多向分化潜能的细胞.胚胎干细胞可以模拟体内发育过程,在无外界信号分子刺激的情况下,自发向神经前体细胞分化.有研究表明,这一体外发育过程受神经分化相关转录因子和表观遗传修饰的共同调控,然而该过程中的分子机制尚不清楚.本研究发现长链非编码RNA1230(LincRNA1230)参与了小鼠(Mus musculus)胚胎干细胞向神经前体细胞的分化过程.在小鼠的胚胎干细胞中过表达LincRNA1230可以显著抑制其神经分化效率;反之,干扰LincRNA1230可以提高分化效率.进一步研究表明,LincRNA1230通过结合Wdr5,降低神经分化相关基因启动子区H3K4me3的修饰水平,从而抑制相关基因的表达活性.这些发现揭示了LincRNA1230在小鼠胚胎干细胞神经分化过程中的重要作用.

关键词：小鼠胚胎干细胞神经分化长链非编码RNA 双价修饰 Wdr5

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