Roles of the Rlim-Rex1 axis during X chromosome inactivation in mice

Feng Wang, Ashmita Chander, Yeonsoo Yoon, Janelle M. Welton, Mary C. Wallingford, Carmen Espejo-Serrano, Francisco Bustos, Greg M. Findlay, Jesse Mager, Ingolf Bach (Lead / Corresponding author)

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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.

Original languageEnglish
Article numbere2313200120
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume120
Issue number52
Early online date19 Dec 2023
DOIs
Publication statusPublished - 26 Dec 2023

Keywords

  • extraembryonic ectoderm
  • implantation
  • Rex1/Zfp42
  • Rlim/Rnf12
  • X chromosome inactivation

ASJC Scopus subject areas

  • General

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