Dynamics of transcription-mediated conversion from euchromatin to facultative heterochromatin at the Xist promoter by Tsix
Dynamics of transcription-mediated conversion from euchromatin to facultative heterochromatin at the Xist promoter by Tsix
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Tsix 在 Xist 启动子处转录介导的从常染色质到兼性异染色质的转化动力学
DOI：
10.1016/j.celrep.2021.108912
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发表时间：
2021
期刊：
影响因子：
8.8
通讯作者：
Kitagawa Masatoshi
中科院分区：
文献类型：
--
作者：
Ohhata Tatsuya;Yamazawa Kazuki;Miura-Kamio Asuka;Takahashi Saori;Sakai Satoshi;Tamura Yuka;Uchida Chiharu;Kitagawa Kyoko;Niida Hiroyuki;Hiratani Ichiro;Kobayashi Hisato;Kimura Hiroshi;Wutz Anton;Kitagawa Masatoshi
从常染色质（EC）到兼性异染色质（fHC）的精细尺度动力学在很大程度上仍然不清楚。在这里，我们集中在Xi和它的沉默启动子Tsix作为转录介导的转换从EC到fHC的范例。在小鼠上胚层干细胞中，Tsix的诱导再现了Xist启动子的转化。调查的动力学表明，转换的进展，在一个逐步的方式。最初，观察到瞬时开放的染色质结构。在第二步中，启动基因沉默并依赖于Tsix，这是可逆的，并伴随着多个组蛋白修饰的同时变化。在最后一步，沉默的维持变得不依赖于Tsix和不可逆，这与核小体占据转录起始位点的-1位置和DNA甲基化引入的开始有关。这项研究强调了逐步基因沉默建立后多个染色质事件的层次结构。
The fine-scale dynamics from euchromatin (EC) to facultative heterochromatin (fHC) has remained largely unclear. Here, we focus onXistand its silencing initiatorTsixas a paradigm of transcription-mediated conversion from EC to fHC. In mouse epiblast stem cells, induction ofTsixrecapitulates the conversion at theXistpromoter. Investigating the dynamics reveals that the conversion proceeds in a stepwise manner. Initially, a transient opened chromatin structure is observed. In the second step, gene silencing is initiated and dependent onTsix, which is reversible and accompanied by simultaneous changes in multiple histone modifications. At the last step, maintenance of silencing becomes independent ofTsixand irreversible, which correlates with occupation of the −1 position of the transcription start site by a nucleosome and initiation of DNA methylation introduction. This study highlights the hierarchy of multiple chromatin events upon stepwise gene silencing establishment.