%0 Journal Article %T Krüppel-like factor 5 rewires NANOG regulatory network to activate human naive pluripotency specific LTR7Ys and promote naive pluripotency. %A Ai Z %A Xiang X %A Xiang Y %A Szczerbinska I %A Qian Y %A Xu X %A Ma C %A Su Y %A Gao B %A Shen H %A Bin Ramli MN %A Chen D %A Liu Y %A Hao JJ %A Ng HH %A Zhang D %A Chan YS %A Liu W %A Liang H %A Ai Z %A Xiang X %A Xiang Y %A Szczerbinska I %A Qian Y %A Xu X %A Ma C %A Su Y %A Gao B %A Shen H %A Bin Ramli MN %A Chen D %A Liu Y %A Hao JJ %A Ng HH %A Zhang D %A Chan YS %A Liu W %A Liang H %A Ai Z %A Xiang X %A Xiang Y %A Szczerbinska I %A Qian Y %A Xu X %A Ma C %A Su Y %A Gao B %A Shen H %A Bin Ramli MN %A Chen D %A Liu Y %A Hao JJ %A Ng HH %A Zhang D %A Chan YS %A Liu W %A Liang H %J Cell Rep %V 40 %N 8 %D Aug 2022 23 %M 36001968 暂无%R 10.1016/j.celrep.2022.111240 %X 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.