Ohhata T, Hoki Y, Sasaki H, Sado T
PRESTO, Japan Science and Technology Agency, Saitama, Japan.
Cytogenet Genome Res. 2006;113(1-4):345-9. doi: 10.1159/000090851.
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.
X 连锁非编码 Xist 基因的差异诱导是雌性哺乳动物胚胎中发生的 X 染色体失活过程中的关键事件。Xist 通过染色质结构修饰在顺式作用下受到其反义基因 Tsix 的负调控。母本 Xist 等位基因通常在外胚层谱系中沉默，当 Tsix 在同一条染色体上被破坏时会异位激活，随后母本 X 染色体即使在雄性胚胎的外胚层谱系中也会发生失活。然而，雄性中单个 Tsix 缺陷的 X 染色体（XΔTsix）在胚胎谱系中是否也会失活仍不清楚。在这里，我们表明，如果外胚层组织由野生型四倍体细胞补充，携带母本来源的 XΔTsix 的雄性和雌性胚胎都可以存活。此外，XΔTsix 上的 Xist 在成年雄性体细胞的 CpG 位点被正确沉默并甲基化。这些结果表明，母本 XΔTsix 导致的胚胎致死性完全归因于外胚层谱系中的缺陷。XΔTsix 在雄性胚胎谱系中似乎不会发生失活，这表明在胚胎谱系中存在一种不依赖 Tsix 的 Xist 沉默机制。
