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Nat Commun. 2018 Nov 12;9(1):4752. doi: 10.1038/s41467-018-07060-w.

REX1 is the critical target of RNF12 in imprinted X chromosome inactivation in mice.

Author information

1
Department of Developmental Biology, Oncode Institute, Erasmus MC, PO Box 2040, 3000, CA, Rotterdam, The Netherlands.
2
Center for Proteomics, Erasmus MC, PO Box 2040, 3000, CA, Rotterdam, The Netherlands.
3
Department of Developmental Biology, Oncode Institute, Erasmus MC, PO Box 2040, 3000, CA, Rotterdam, The Netherlands. j.gribnau@erasmusmc.nl.

Abstract

In mice, imprinted X chromosome inactivation (iXCI) of the paternal X in the pre-implantation embryo and extraembryonic tissues is followed by X reactivation in the inner cell mass (ICM) of the blastocyst to facilitate initiation of random XCI (rXCI) in all embryonic tissues. RNF12 is an E3 ubiquitin ligase that plays a key role in XCI. RNF12 targets pluripotency protein REX1 for degradation to initiate rXCI in embryonic stem cells (ESCs) and loss of the maternal copy of Rnf12 leads to embryonic lethality due to iXCI failure. Here, we show that loss of Rex1 rescues the rXCI phenotype observed in Rnf12-/- ESCs, and that REX1 is the prime target of RNF12 in ESCs. Genetic ablation of Rex1 in Rnf12-/- mice rescues the Rnf12-/- iXCI phenotype, and results in viable and fertile Rnf12-/-:Rex1-/- female mice displaying normal iXCI and rXCI. Our results show that REX1 is the critical target of RNF12 in XCI.

PMID:
30420655
PMCID:
PMC6232137
DOI:
10.1038/s41467-018-07060-w
[Indexed for MEDLINE]
Free PMC Article

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