Maternal Rnf12/RLIM is required for imprinted X-chromosome inactivation in mice

Jongdae Shin, Michael Bossenz, Young Chung, Hong Ma, Meg Byron, Naoko Taniguchi-Ishigaki, Xiaochun Zhu, Baowei Jiao, Lisa L. Hall, Michael R. Green, Stephen N. Jones, Irm Hermans-Borgmeyer, Jeanne B. Lawrence, Ingolf Bach

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108 Scopus citations

Abstract

Two forms of X-chromosome inactivation (XCI) ensure the selective silencing of female sex chromosomes during mouse embryogenesis. Imprinted XCI begins with the detection of Xist RNA expression on the paternal X chromosome (Xp) at about the four-cell stage of embryonic development. In the embryonic tissues of the inner cell mass, a random form of XCI occurs in blastocysts that inactivates either Xp or the maternal X chromosome (Xm). Both forms of XCI require the non-coding Xist RNA that coats the inactive X chromosome from which it is expressed. Xist has crucial functions in the silencing of X-linked genes, including Rnf12 (refs 3, 4) encoding the ubiquitin ligase RLIM (RING finger LIM-domain-interacting protein). Here we show, by targeting a conditional knockout of Rnf12 to oocytes where RLIM accumulates to high levels, that the maternal transmission of the mutant X chromosome (β "m) leads to lethality in female embryos as a result of defective imprinted XCI. We provide evidence that in β "m female embryos the initial formation of Xist clouds and Xp silencing are inhibited. In contrast, embryonic stem cells lacking RLIM are able to form Xist clouds and silence at least some X-linked genes during random XCI. These results assign crucial functions to the maternal deposit of Rnf12/RLIM for the initiation of imprinted XCI.

Original languageEnglish (US)
Pages (from-to)977-981
Number of pages5
JournalNature
Volume467
Issue number7318
DOIs
StatePublished - Oct 21 2010

All Science Journal Classification (ASJC) codes

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    Shin, J., Bossenz, M., Chung, Y., Ma, H., Byron, M., Taniguchi-Ishigaki, N., Zhu, X., Jiao, B., Hall, L. L., Green, M. R., Jones, S. N., Hermans-Borgmeyer, I., Lawrence, J. B., & Bach, I. (2010). Maternal Rnf12/RLIM is required for imprinted X-chromosome inactivation in mice. Nature, 467(7318), 977-981. https://doi.org/10.1038/nature09457