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论文题目: Activin/Smad2-induced Histone H3 Lys-27 Trimethylation (H3K27me3) Reduction Is Crucial to Initiate Mesendoderm Differentiation of Human Embryonic Stem Cells
英文论文题目: Activin/Smad2-induced Histone H3 Lys-27 Trimethylation (H3K27me3) Reduction Is Crucial to Initiate Mesendoderm Differentiation of Human Embryonic Stem Cells
第一作者: Wang, L; Xu, XH; Cao, YQ; Li, ZW; Cheng, H; Zhu, GY; Duan, FY; Na, J; Han, JDJ; Chen, YG
英文第一作者: Wang, L; Xu, XH; Cao, YQ; Li, ZW; Cheng, H; Zhu, GY; Duan, FY; Na, J; Han, JDJ; Chen, YG
联系作者: Chen, YG (reprint author), Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, State Key Lab Membrane Biol, Beijing 100084, Peoples R China.
英文联系作者: Chen, YG (reprint author), Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, State Key Lab Membrane Biol, Beijing 100084, Peoples R China.
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发表年度: 2017
卷: 292
期: 4
页码: 1339-+
摘要: 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.
英文摘要: 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.
刊物名称: JOURNAL OF BIOLOGICAL CHEMISTRY
英文刊物名称: JOURNAL OF BIOLOGICAL CHEMISTRY
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学科: Biochemistry & Molecular Biology
英文学科: Biochemistry & Molecular Biology
影响因子: 4.125
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论文类别: Article
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