日本京都大学人类生物学高级研究所（ASHBi）Mitinori Saitou研究团队取得一项新突破。他们发现食蟹猴发育过程中X染色体剂量补偿程序。2021年11月19日出版的《科学》杂志发表了这项成果。

他们阐明了食蟹猴 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活跃的中间轴承抑制修饰和压缩结构在着床后一周获得 XCI，而羊膜、外胚层和下胚层长期保持这种中间体，在植入后一周获得 XCI。雄性逐渐实现 X 染色体上调 (XCU)，而雌性显示 XCU 与 XCI 一致，两者都在植入后 1 周建立 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 途径而经历 X 染色体再激活。他们的研究结果为阐明灵长类动物（包括人类）的剂量补偿机制奠定了基础。

研究人员表示，X 染色体剂量补偿确保 X 染色体和常染色体之间以及性别之间的平衡基因剂量，涉及哺乳动物之间的不同机制。

附：英文原文

Title: The X chromosome dosage compensation program during the development of cynomolgus monkeys

Author: Ikuhiro Okamoto, Tomonori Nakamura, Kotaro Sasaki, Yukihiro Yabuta, Chizuru Iwatani, Hideaki Tsuchiya, Shin-ichiro Nakamura, Masatsugu Ema, Takuya Yamamoto, Mitinori Saitou

Issue&Volume: 2021-11-19

Abstract: 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.

DOI: abd8887

Source: https://www.science.org/doi/10.1126/science.abd8887