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

被引：29

作者：

Gontan, Cristina ^{[1
]}

Mira-Bontenbal, Hegias ^{[1
]}

Magaraki, Aristea ^{[1
]}

Dupont, Catherine ^{[1
]}

Barakat, Tahsin Stefan ^{[1
]}

Rentmeester, Eveline ^{[1
]}

Demmers, Jeroen ^{[2
]}

Gribnau, Joost ^{[1
]}

机构：

[1] Erasmus MC, Oncode Inst, Dept Dev Biol, POB 2040, NL-3000 CA Rotterdam, Netherlands

[2] Erasmus MC, Ctr Prote, POB 2040, NL-3000 CA Rotterdam, Netherlands

来源：

NATURE COMMUNICATIONS | 2018年 / 9卷

关键词：

CELL-CULTURE SILAC; AMINO-ACIDS; MOUSE; REACTIVATION; ACTIVATOR; RLIM; RNA;

D O I：

10.1038/s41467-018-07060-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

共 35 条

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