Abstract：
Endogenous retroviruses (ERVs) have been reported to participate in pre-implantation development of mammalian embryos. In early human embryogenesis, different ERV sub-families are activated in a highly stage-specific manner. How the specificity of ERV activation is achieved remains largely unknown. Here, we demonstrate the mechanism of how LTR7Ys, the human morula-blastocyst-specific HERVH long terminal repeats, are activated by the naive pluripotency transcription network. We find that KLF5 interacts with and rewires NANOG to bind and regulate LTR7Ys; in contrast, the primed-specific LTR7s are preferentially bound by NANOG in the absence of KLF5. The specific activation of LTR7Ys by KLF5 and NANOG in pluripotent stem cells contributes to human-specific naive pluripotency regulation. KLF5-LTR7Y axis also promotes the expression of trophectoderm genes and contributes to the expanded cell potential toward extra-embryonic lineage. Our study suggests that HERVs are activated by cell-state-specific transcription machinery and promote stage-specific transcription network and cell potency.
摘要：
据报道，内源性逆转录病毒（ERV）参与哺乳动物胚胎的植入前发育。在人类胚胎发育早期,不同的ERV亚家族以高度阶段特异性的方式被激活。如何实现ERV激活的特异性仍然是未知的。这里,我们展示了LTR7Y，人类桑态度-胚泡特异性HERVH长末端重复，被幼稚多能性转录网络激活。我们发现KLF5与NANOG相互作用并重新连接以结合和调节LTR7Y；相反，在不存在KLF5的情况下,引发的特异性LTR7优先被NANOG结合。多能干细胞中KLF5和NANOG对LTR7Y的特异性激活有助于人特异性的幼稚多能性调节。KLF5-LTR7Y轴还促进滋养外胚层基因的表达，并有助于向胚外谱系扩展的细胞潜力。我们的研究表明，HERV被细胞状态特异性转录机制激活，并促进阶段特异性转录网络和细胞效力。
