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

Cell Rep. 2022-08; 
Zhipeng Ai, Xinyu Xiang, Yangquan Xiang, Iwona Szczerbinska, Yuli Qian, Xiao Xu, Chenyang Ma, Yaqi Su, Bing Gao, Hao Shen, Muhammad Nadzim Bin Ramli, Di Chen, Yue Liu, Jia-Jie Hao, Huck Hui Ng, Dan Zhang, Yun-Shen Chan, Wanlu Liu, Hongqing Liang
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摘要

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 pluripote... More

關鍵詞

CP: stem cell research, ERVs, KLFs, cell potency, naive and primed pluripotency, transcription control, trophectoderm
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