RT Journal Article
SR Electronic
T1 Cell autonomous requirement of imprinted XCI in extra-embryonic polar trophoblast cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.10.515976
DO 10.1101/2022.11.10.515976
A1 Wang, Feng
A1 Chander, Ashmita
A1 Yoon, Yeonsoo
A1 Wallingford, Mary C.
A1 Espejo-Serrano, Carmen
A1 Bustos, Francisco
A1 Findlay, Greg M.
A1 Mager, Jesse
A1 Bach, Ingolf
YR 2022
UL http://biorxiv.org/content/early/2022/11/10/2022.11.10.515976.abstract
AB 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) silencing the paternally inherited X chromosome (Xp) is initiated at the 2-4 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) during peri-implantation stages. Lack of X dosage compensation leads to peri-implantation lethality due to inhibition of trophoblast stem cells. However, as the epiblast regulates the trophoblast lineage, the roles of iXCI vs rXCI in the early lethal phenotype remains unclear. We have investigated functions and expression of Rlim (Rnf12), an E3 ubiquitin ligase, and its target protein Rex1 (Zfp42) that control iXCI. Consistent with functions specifically for iXCI, we show an inverse correlation in the expression of Rlim and Rex1 throughout pre-implantation development, but an Rlim-independent downregulation of Rex1 in epiblast cells upon implantation. Moreover, disturbing the functional Rlim-Rex1 dynamics in females leads to cell fate confusion and premature differentiation specifically of the polar trophoblast stem cell pool. Thus, controlled by the Rlim-Rex1 axis, female mouse development requires iXCI in the polar trophoblast cell lineage.Competing Interest StatementThe authors have declared no competing interest.