Xist-dependent imprinted X inactivation and the early developmental consequences of its failure.
Xist-dependent imprinted X inactivation and the early developmental consequences of its failure.
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DOI：
10.1038/nsmb.3365
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发表时间：
2017-03
影响因子：
16.8
通讯作者：
Heard E
中科院分区：
文献类型：
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作者：
Borensztein M;Syx L;Ancelin K;Diabangouaya P;Picard C;Liu T;Liang JB;Vassilev I;Galupa R;Servant N;Barillot E;Surani A;Chen CJ;Heard E
长非编码RNA Xist在小鼠植入前雌性胚胎中仅从父系X染色体表达，并导致其转录沉默。在雌性动物中，Xist缺失导致着床后死亡。在这里，我们报告说，启动印迹XCI绝对需要Xist使用单细胞RNA测序的早期植入前小鼠胚胎。缺乏父源Xist导致早期胚泡中全基因组转录失调，无法激活胚胎外途径，这对植入后发育至关重要。我们还表明，X-连锁基因的表达动力学依赖于应变和父母的起源，以及位置沿着X染色体，特别是在Xist的第一个“入口”网站。这项研究表明，剂量补偿失败早在胚泡阶段就产生了影响，并揭示了遗传和表观遗传在早期胚胎发生过程中协调X染色体转录沉默的贡献。
The long non-coding RNA Xist is only expressed from the paternal X chromosome in mouse pre-implantation female embryos and leads to its transcriptional silencing. In females, absence of Xist leads to post-implantation lethality. Here we report that the initiation of imprinted XCI absolutely requires Xist using single-cell RNA-sequencing of early pre-implantation mouse embryos. Lack of paternal Xist leads to genome-wide transcriptional misregulation in the early blastocyst, with failure to activate the extra-embryonic pathway that is essential for post-implantation development. We also demonstrate that the expression dynamics of X-linked genes depends both on strain and parent-of-origin, as well as on location along the X chromosome, particularly at Xist’s first “entry” sites. This study demonstrates that dosage compensation failure has an impact as early as the blastocyst stage and reveals genetic and epigenetic contributions in orchestrating the transcriptional silencing of the X chromosome during early embryogenesis.