{Reference Type}: Journal Article
{Title}: Krüppel-like factor 5 rewires NANOG regulatory network to activate human naive pluripotency specific LTR7Ys and promote naive pluripotency.
{Author}: Ai Z;Xiang X;Xiang Y;Szczerbinska I;Qian Y;Xu X;Ma C;Su Y;Gao B;Shen H;Bin Ramli MN;Chen D;Liu Y;Hao JJ;Ng HH;Zhang D;Chan YS;Liu W;Liang H;Ai Z;Xiang X;Xiang Y;Szczerbinska I;Qian Y;Xu X;Ma C;Su Y;Gao B;Shen H;Bin Ramli MN;Chen D;Liu Y;Hao JJ;Ng HH;Zhang D;Chan YS;Liu W;Liang H;Ai Z;Xiang X;Xiang Y;Szczerbinska I;Qian Y;Xu X;Ma C;Su Y;Gao B;Shen H;Bin Ramli MN;Chen D;Liu Y;Hao JJ;Ng HH;Zhang D;Chan YS;Liu W;Liang H;
{Journal}: Cell Rep
{Volume}: 40
{Issue}: 8
{Year}: Aug 2022 23
暂无{DOI}: 10.1016/j.celrep.2022.111240
{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.