Maternal Rnf12/RLIM is required for imprinted X-chromosome inactivation in mice
Department of Cell Biology; Program in Gene Function and Expression; Program in Molecular Medicine
Animals; Animals, Congenic; Blastocyst; Cell Line; Chromosomes, Mammalian; Embryo Loss; Fathers; Female; Gene Silencing; *Genomic Imprinting; Male; Mice; Mice, Transgenic; *Mothers; RNA, Untranslated; Repressor Proteins; X Chromosome; X Chromosome Inactivation
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 (Deltam) leads to lethality in female embryos as a result of defective imprinted XCI. We provide evidence that in Deltam 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.
DOI of Published Version
Nature. 2010 Oct 21;467(7318):977-81. Link to article on publisher's site
Shin, JongDae; Bossenz, Michael; Chung, Young; Ma, Hong; Byron, Meg; Taniguchi-Ishigaki, Naoko; Zhu, Xiaochun; Baowei, Jiao; Hall, Lisa L.; Green, Michael R.; Jones, Stephen N.; Hermans-Borgmeyer, Irm; Lawrence, Jeanne B.; and Bach, Ingolf, "Maternal Rnf12/RLIM is required for imprinted X-chromosome inactivation in mice" (2010). Stephen Jones Lab Publications. 2.