A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity.
A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity.
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DOI：
10.1016/j.cell.2018.05.043
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发表时间：
2018-07-12
期刊：
影响因子：
64.5
通讯作者：
Ramalho-Santos M
中科院分区：
文献类型：
--
作者：
Percharde M;Lin CJ;Yin Y;Guan J;Peixoto GA;Bulut-Karslioglu A;Biechele S;Huang B;Shen X;Ramalho-Santos M
转座因子占哺乳动物基因组的近一半，通常被描述为寄生虫或“垃圾DNA”。LINE 1逆转录转座子是最丰富的一类，被认为是有害的细胞，但矛盾的是，在早期发育过程中高度表达。在这里，我们报告LINE 1在小鼠胚胎干（ES）细胞和植入前胚胎中起着重要作用。在ES细胞中，LINE 1作为核RNA支架，招募核仁素和Kap 1/Trim 28来抑制Dux，Dux是2细胞胚胎特异性转录程序的主激活因子。同时，LINE 1 RNA介导核仁素和Kap 1与rDNA的结合，促进rRNA合成和ES细胞自我更新。在胚胎中，LINE 1 RNA是Dux沉默、rRNA合成和退出2细胞阶段所必需的。结果揭示了LINE 1 RNA，核仁蛋白，Kap 1和核仁周围染色质在转录，发育潜能和ES细胞自我更新的调节中的重要伙伴关系。LINE 1元件衍生的RNA在早期胚胎发育期间高度表达，作为核支架促进必需基因表达程序
Transposable elements represent nearly half of mammalian genomes and are generally described as parasites or ‘junk DNA’. The LINE1 retrotransposon is the most abundant class and is thought to be deleterious for cells, yet is paradoxically highly expressed during early development. Here we report that LINE1 plays essential roles in mouse embryonic stem (ES) cells and pre-implantation embryos. In ES cells, LINE1 acts as a nuclear RNA scaffold that recruits Nucleolin and Kap1/Trim28 to repress Dux, the master activator of a transcriptional program specific to the 2-cell embryo. In parallel, LINE1 RNA mediates binding of Nucleolin and Kap1 to rDNA, promoting rRNA synthesis and ES cell self-renewal. In embryos, LINE1 RNA is required for Dux silencing, synthesis of rRNA and exit from the 2-cell stage. The results reveal an essential partnership between LINE1 RNA, Nucleolin, Kap1 and peri-nucleolar chromatin in the regulation of transcription, developmental potency and ES cell self-renewal. Highly expressed during early embryonic development, LINE1 element-derived RNA acts as a nuclear scaffold to facilitate essential gene expression programs
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