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论文题目: PHB Associates with the HIRA Complex to Control an Epigenetic-Metabolic Circuit in Human ESCs
英文论文题目: PHB Associates with the HIRA Complex to Control an Epigenetic-Metabolic Circuit in Human ESCs
第一作者: Zhu, ZX; Li, CL; Zeng, YW; Ding, JY; Qu, ZP; Gu, JJ; Ge, LX; Tang, F; Huang, X; Zhou, CL; Wang, P; Zheng, DY; Jin, Y
英文第一作者: Zhu, ZX; Li, CL; Zeng, YW; Ding, JY; Qu, ZP; Gu, JJ; Ge, LX; Tang, F; Huang, X; Zhou, CL; Wang, P; Zheng, DY; Jin, Y
联系作者: Jin, Y (reprint author), Shanghai Jiao Tong Univ, Key Lab Stem Cell Biol, Chinese Acad Sci, Inst Hlth Sci,Shanghai Inst Biol Sci,Sch Med, Peoples R China.
英文联系作者: Jin, Y (reprint author), Shanghai Jiao Tong Univ, Key Lab Stem Cell Biol, Chinese Acad Sci, Inst Hlth Sci,Shanghai Inst Biol Sci,Sch Med, Peoples R China.
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发表年度: 2017
卷: 20
期: 2
页码: 274-+
摘要: The chromatin landscape and cellular metabolism both contribute to cell fate determination, but their interplay remains poorly understood. Using genome-wide siRNA screening, we have identified prohibitin (PHB) as an essential factor in self-renewal of human embryonic stem cells (hESCs). Mechanistically, PHB forms protein complexes with HIRA, a histone H3.3 chaperone, and stabilizes the protein levels of HIRA complex components. Like PHB, HIRA is required for hESC self-renewal. PHB and HIRA act together to control global deposition of histone H3.3 and gene expression in hESCs. Of particular note, PHB and HIRA regulate the chromatin architecture at the promoters of isocitrate dehydrogenase genes to promote transcription and, thus, production of a-ketoglutarate, a key metabolite in the regulation of ESC fate. Our study shows that PHB has an unexpected nuclear role in hESCs that is required for self-renewal and that it acts with HIRA in chromatin organization to link epigenetic organization to a metabolic circuit.
英文摘要: The chromatin landscape and cellular metabolism both contribute to cell fate determination, but their interplay remains poorly understood. Using genome-wide siRNA screening, we have identified prohibitin (PHB) as an essential factor in self-renewal of human embryonic stem cells (hESCs). Mechanistically, PHB forms protein complexes with HIRA, a histone H3.3 chaperone, and stabilizes the protein levels of HIRA complex components. Like PHB, HIRA is required for hESC self-renewal. PHB and HIRA act together to control global deposition of histone H3.3 and gene expression in hESCs. Of particular note, PHB and HIRA regulate the chromatin architecture at the promoters of isocitrate dehydrogenase genes to promote transcription and, thus, production of a-ketoglutarate, a key metabolite in the regulation of ESC fate. Our study shows that PHB has an unexpected nuclear role in hESCs that is required for self-renewal and that it acts with HIRA in chromatin organization to link epigenetic organization to a metabolic circuit.
刊物名称: CELL STEM CELL
英文刊物名称: CELL STEM CELL
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学科: Cell & Tissue Engineering; Cell Biology
英文学科: Cell & Tissue Engineering; Cell Biology
影响因子: 23.394
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论文类别: Article
英文论文类别: Article
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