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The Journal of biological chemistry v.292 no.4, 2017년, pp.1339 - 1350   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Activin/Smad2-induced Histone H3 Lys-27 Trimethylation (H3K27me3) Reduction Is Crucial to Initiate Mesendoderm Differentiation of Human Embryonic Stem Cells

Wang, Lu (From the State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China, ) ; Xu, Xuanhao (From the State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China, ) ; Cao, Yaqiang (the Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China, and ) ; Li, Zhongwei (From the State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China, ) ; Cheng, Hao (the Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Science ) ; Zhu, Gaoyang ; Duan, Fuyu ; Na, Jie ; Han, Jing-Dong J. ; Chen, Ye-Guang ;
  • 초록  

    Differentiation of human embryonic stem cells into mesendoderm (ME) is directed by extrinsic signals and intrinsic epigenetic modifications. However, the dynamics of these epigenetic modifications and the mechanisms by which extrinsic signals regulate the epigenetic modifications during the initiation of ME differentiation remain elusive. In this study, we report that levels of histone H3 Lys-27 trimethylation (H3K27me3) decrease during ME initiation, which is essential for subsequent differentiation induced by the combined effects of activin and Wnt signaling. Furthermore, we demonstrate that activin mediates the H3K27me3 decrease via the Smad2-mediated reduction of EZH2 protein level. Our results suggest a two-step process of ME initiation: first, epigenetic priming via removal of H3K27me3 marks and, second, transcription activation. Our findings demonstrate a critical role of H3K27me3 priming and a direct interaction between extrinsic signals and epigenetic modifications during ME initiation.


  • 주제어

    activin .   chromatin modification .   embryonic stem cell .   SMAD transcription factor .   Wnt signaling .   H3K27me3 .   Mesendoderm .   PRC2.  

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