A novel Xist RNA-mediated chromosome inactivation model using a mouse artificial chromosome
A novel Xist RNA-mediated chromosome inactivation model using a mouse artificial chromosome
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DOI：
10.1007/s10529-020-02826-z
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发表时间：
2020-01-31
影响因子：
2.7
通讯作者：
Kugoh, Hiroyuki
中科院分区：
文献类型：
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作者：
Inaoka, Daigo;Sunamura, Naohiro;Kugoh, Hiroyuki
目的构建携带小鼠Xist基因（X-inactive specific transcript，Xist-MAC）的小鼠人工染色体，为体外系统研究Xist RNA介导的染色体失活奠定基础。结果Xist基因在CHO细胞中的异位表达导致Xist RNA在MAC上的顺式积累。此外，通过微细胞介导的染色体转移将Xist-MAC引入来自雄性小鼠的胚胎干细胞导致Xist RNA在MAC上顺式积累。在分化状态下观察到染色体失活。此外，这种现象伴随着H3 K27三甲基化的表观遗传修饰。结论成功构建了一种新的染色体失活模型Xist-MAC，为X染色体失活相关基因和蛋白的筛选和功能分析提供了一个有价值的工具。
Objective To develop a mouse artificial chromosome (MAC) carrying the mouse Xist gene (X-inactive specific transcript; Xist-MAC) as a systematic in vitro approach for investigating Xist RNA-mediated chromosome inactivation. Results Ectopic expression of the Xist gene in CHO cells led to the accumulation of Xist RNA in cis on the MAC. In addition, the introduction of Xist-MAC to embryonic stem cells from male mice via microcell-mediated chromosome transfer resulted in the accumulation of Xist RNA in cis on the MAC. Chromosomal inactivation was observed in the differentiated state. Moreover, this phenomenon was accompanied by the epigenetic modification of H3K27 trimethylation. Conclusions We successfully generated a novel chromosome inactivation model, Xist-MAC, which will provide a valuable tool for the screening and functional analysis of X chromosome inactivation-related genes and proteins.