First Author | Wang F | Year | 2023 |
Journal | Proc Natl Acad Sci U S A | Volume | 120 |
Issue | 52 | Pages | e2313200120 |
PubMed ID | 38113263 | Mgi Jnum | J:345819 |
Mgi Id | MGI:7610937 | Doi | 10.1073/pnas.2313200120 |
Citation | Wang F, et al. (2023) Roles of the Rlim-Rex1 axis during X chromosome inactivation in mice. Proc Natl Acad Sci U S A 120(52):e2313200120 |
abstractText | 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. |