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染色质地貌和细胞代谢对细胞命运决定有着重要的作用,但人们对它们之间的互相作用却了解甚少。我们运用基因组范围的si RNA筛选,发现PHB对于维持人胚胎干细胞的自我更新具有重要的作用。其具体机制如下:PHB可以和H3.3的伴侣蛋白HIRA形成蛋白复合体;与PHB相似的是,HIRA对人胚胎干细胞特性的维持也起着重要的作用;特别是PHB和HIRA对异柠檬酸脱氢酶启动子区域染色质结构的调节,调控着对胚胎干细胞命运有着重要作用的代谢产物—α-酮戊二酸的产生。我们的研究揭示了在人胚胎干细胞的细胞核中,PHB通过与HIRA复合体相互作用参与维持正常染色质的结构和重要代谢产物的生成,进而使人胚胎干细胞处于自我更新状态。
Chromatin geomorphology and cellular metabolism play an important role in determining the fate of cells, but little is known about the interaction between them. Using genome-wide si RNA screening, we found that PHB plays an important role in maintaining self-renewal of human embryonic stem cells. The specific mechanism is as follows: PHB can form a protein complex with H3.3’s partner protein HIRA; similarly to PHB, HIRA also plays an important role in maintaining the characteristics of human embryonic stem cells; in particular, PHB and HIRA affect isocitrate The regulation of chromatin structure in the promoter region of dehydrogenase regulates the production of α-ketoglutarate, an important metabolite of embryonic stem cells. Our study revealed that in the nucleus of human embryonic stem cells, PHB is involved in maintaining the structure of the normal chromatin and the production of important metabolites by interacting with the HIRA complex, thereby allowing the human embryonic stem cells to be self-renewing.