外胚层
生物
泛素连接酶
西斯特
X-失活
细胞生物学
胚胎
胚胎干细胞
诺金
抑制因子
雷克斯1
遗传学
基因
胚胎发生
X染色体
泛素
基因表达
原肠化
诱导多能干细胞
骨形态发生蛋白
作者
Feng Wang,Ashmita Chander,Yeonsoo Yoon,Janelle M. Welton,Mary C. Wallingford,Carmen Espejo-Serrano,Francisco Bustos,Greg M. Findlay,Jesse Mager,Ingolf Bach
标识
DOI:10.1073/pnas.2313200120
摘要
In female mice, the gene dosage from X chromosomes is adjusted by a process called X chromosome inactivation (XCI) that occurs in two steps. An imprinted form of XCI (iXCI) that silences the paternally inherited X chromosome (Xp) is initiated at the 2- to 4-cell stages. As extraembryonic cells including trophoblasts keep the Xp silenced, epiblast cells that give rise to the embryo proper reactivate the Xp and undergo a random form of XCI (rXCI) around implantation. Both iXCI and rXCI require the lncRNA Xist , which is expressed from the X to be inactivated. The X-linked E3 ubiquitin ligase Rlim (Rnf12) in conjunction with its target protein Rex1 (Zfp42), a critical repressor of Xist , have emerged as major regulators of iXCI. However, their roles in rXCI remain controversial. Investigating early mouse development, we show that the Rlim–Rex1 axis is active in pre-implantation embryos. Upon implantation Rex1 levels are downregulated independently of Rlim specifically in epiblast cells. These results provide a conceptual framework of how the functional dynamics between Rlim and Rex1 ensures regulation of iXCI but not rXCI in female mice.
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