Roles of the Rlim-Rex1 axis during X chromosome inactivation in mice.
Proc Natl Acad Sci U S A
; 120(52): e2313200120, 2023 Dec 26.
Article
em En
| MEDLINE
| ID: mdl-38113263
ABSTRACT
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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MEDLINE
Assunto principal:
Inativação do Cromossomo X
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RNA Longo não Codificante
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article