Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Science. 2021 Nov 19;374(6570):eabd8887. doi: 10.1126/science.abd8887.
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.
X 染色体剂量补偿确保了 X 染色体与常染色体之间以及性别之间的基因剂量平衡，涉及哺乳动物中不同的机制。我们阐明了食蟹猴（一种人类发育的模型）中 X 染色体失活（XCI）的一种独特机制。滋养外胚层和细胞滋养层在着床前后通过带有抑制性修饰和紧凑结构的活跃中间体获得 XCI，而羊膜、上胚层和下胚层则长时间维持这种中间体，在着床后一周达到 XCI。雄性逐渐实现 X 染色体上调（XCU），而雌性则与 XCI 同时发生 XCU，两者均在着床后一周左右建立 X：常染色体剂量补偿。相反，原始生殖细胞通过在其发育早期逆转 XCI 途径来重新激活 X 染色体。我们的发现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。
