Tsix silences Xist through modification of chromatin structure
Tsix silences Xist through modification of chromatin structure
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DOI：
10.1016/j.devcel.2005.05.015
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发表时间：
2005-07-01
影响因子：
11.8
通讯作者：
Sasaki, H
中科院分区：
文献类型：
--
作者：
Sado, T;Hoki, Y;Sasaki, H
X失活由Xist及其反义基因Tsix控制，两者都不编码蛋白质。Xist是X失活发生顺式所必需的，其差异表达是X失活启动的关键事件。Xist和Tsix被印迹在小鼠胚胎的胚外组织中，使得它们分别从父体和母体X表达，导致父体X的优先失活。靶向破坏Tsix导致Xist的异位表达，表明Tsix顺式负调控Xist。然而，这种反义调控的分子机制仍然未知。在这里，我们表明，Tsix转录沉默Xist在胚胎和胚胎外组织的小鼠胚胎。此外，我们表明，Tsix的破坏损害建立抑制性表观遗传修饰和染色质结构在Xist基因座。我们建议，Tsix沉默Xist通过修改染色质结构。
X inactivation is controlled by Xist and its antisense gene, Tsix, neither of which encodes a protein. Xist is essential for X inactivation to occur in cis, and its differential expression is a key event in the initiation of X inactivation. Xist and Tsix are imprinted in the extraembryonic tissues of mouse embryos so that they are expressed from the paternal and maternal X, respectively, resulting in the preferential inactivation of the paternal X. Targeted disruption of Tsix causes ectopic expression of Xist, suggesting that Tsix negatively regulates Xist in cis. However, the molecular mechanism of this antisense regulation remains unknown. Here, we demonstrate that Tsix transcriptionally silences Xist in both embryonic and extraembryonic tissues of mouse embryos. Moreover, we show that disruption of Tsix impairs establishment of repressive epigenetic modifications and chromatin structure at the Xist locus. We propose that Tsix silences Xist through modification of the chromatin structure.