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The X chromosome dosage compensation program during the development of cynomolgus monkeys
Science ( IF 44.7 ) Pub Date : 2021-11-19 , DOI: 10.1126/science.abd8887
Ikuhiro Okamoto 1, 2 , Tomonori Nakamura 1, 2, 3 , Kotaro Sasaki 2 , Yukihiro Yabuta 1, 2 , Chizuru Iwatani 4 , Hideaki Tsuchiya 4 , Shin-Ichiro Nakamura 4 , Masatsugu Ema 1, 4 , Takuya Yamamoto 1, 5, 6, 7 , Mitinori Saitou 1, 2, 5
Affiliation  

X chromosome dosage compensation ensures balanced gene dosage between the X chromosome and autosomes and between the sexes, involving divergent mechanisms among mammals. We elucidated a distinct mechanism for X chromosome inactivation (XCI) in cynomolgus monkeys, a model for human development. The trophectoderm and cytotrophoblast acquire XCI around implantation through an active intermediate bearing repressive modifications and compacted structure, whereas the amnion, epiblast, and hypoblast maintain such an intermediate protractedly, attaining XCI by a week after implantation. Males achieve X chromosome up-regulation (XCU) progressively, whereas females show XCU coincidentally with XCI, both establishing the X:autosome dosage compensation by 1 week after implantation. Conversely, primordial germ cells undergo X chromosome reactivation by reversing the XCI pathway early during their development. Our findings establish a foundation for clarifying the dosage compensation mechanisms in primates, including humans.

中文翻译:

食蟹猴发育过程中的X染色体剂量补偿程序

X 染色体剂量补偿确保 X 染色体与常染色体和两性之间的基因剂量平衡,涉及哺乳动物之间的不同机制。我们阐明了食蟹猴中 X 染色体失活 (XCI) 的独特机制,食蟹猴是人类发育的模型。滋养外胚层和细胞滋养层通过具有抑制性修饰和致密结构的活性中间体在植入前后获得 XCI,而羊膜、外胚层和下胚层长期维持这种中间体,在植入后一周达到 XCI。男性逐渐实现 X 染色体上调 (XCU),而女性显示 XCU 与 XCI 巧合,两者均在植入后 1 周建立 X:常染色体剂量补偿。反过来,原始生殖细胞在发育早期通过逆转 XCI 途径进行 X 染色体再激活。我们的研究结果为阐明包括人类在内的灵长类动物的剂量补偿机制奠定了基础。
更新日期:2021-11-19
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