Tsix-deficient X chromosome does not undergo inactivation in the embryonic lineage in males: implications for Tsix-independent silencing of Xist.
Differential induction of the X-linked non-coding Xist gene is a key event in the process of X inactivation occurring in female mammalian embryos. Xist is negatively regulated in cis by its antisense gene Tsix through modification of the chromatin structure. The maternal Xist allele, which is normally silent in the extraembryonic lineages, is ectopically activated when Tsix is disrupted on the same chromosome, and subsequently the maternal X chromosome undergoes inactivation in the extraembryonic lineages even in males. However, it is still unknown whether the single Tsix-deficient X chromosome (XDeltaTsix) in males is also inactivated in the embryonic lineage. Here, we show that both male and female embryos carrying a maternally derived XDeltaTsix could survive if the extraembryonic tissues were complemented by wild-type tetraploid cells. In addition, Xist on the XDeltaTsix was properly silenced and methylated at CpG sites in adult male somatic cells. These results indicate that the embryonic lethality caused by the maternal XDeltaTsix is solely attributable to the defects in the extraembryonic lineages. XDeltaTsix does not seem to undergo inactivation in the embryonic lineage in males, suggesting the presence of a Tsix-independent silencing mechanism for Xist in the embryonic lineage.
PRESTO, Japan Science and Technology Agency, Saitama, Japan.
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Ohhata
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Hoki
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Sasaki
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Sado
D000818:Animals; D001483:Base Sequence; D001755:Blastocyst / Q000502:physiology; D017931:DNA Primers; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D005838:Genotype; D008297:Male; D051379:Mice; D011123:Polyploidy; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D013480:Superovulation
D017931:DNA Primers; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C465658:Tsix transcript, mouse; C077885:XIST non-coding RNA