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 ge...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.展开更多
基金This work was supported by grants from the Ministry of Science and Technology （2016YFA0101300）, the National Natural Science Foundation of China （81530042, 31210103905, 31371510, 31571529, 31571519, 31471250, and 31571390）, the Science and Technology Commission of Shanghai Municipality （15JC1403201）, and the Fundamental Research Funds for the Central Universities （2000219136 and 1500219106）.
文摘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.
