Krüppel-like factor 5 rewires NANOG regulatory network to activate human naive pluripotency specific LTR7Ys and promote naive pluripotency

• DOI: 10.1016/j.celrep.2022.111240
• Publication Date: 2022-08-23T14:33:30Z
• Authors: Zhipeng Ai; Xinyu Xiang; Yangquan Xiang; Iwona Szczerbinska; Yuli Qian; Xiao Xu; Chenyang Ma; Yaqi Su; Bing Gao; Hao Shen; Muhammad Nadzim B...; Di Chen; Yue Liu; Jia-jie Hao; Huck Hui Ng; Dan Zhang; Yun-Shen Chan; Wanlu Liu; Hongqing Liang
• Keywords: Homeobox protein NANOG; Nanog Homeobox Protein; Rex1

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 a highly stage-specific manner. How the specificity activation is achieved remains largely unknown. Here, we demonstrate mechanism how LTR7Ys, morula-blastocyst-specific HERVH long terminal repeats, by naive pluripotency transcription network. We find that KLF5 interacts with and rewires NANOG bind regulate LTR7Ys; contrast, primed-specific LTR7s preferentially bound absence KLF5. The specific LTR7Ys pluripotent stem cells contributes human-specific regulation. KLF5-LTR7Y axis also promotes expression trophectoderm genes expanded cell potential toward extra-embryonic lineage. Our study suggests HERVs cell-state-specific machinery promote network potency.