Tsix-mediated epigenetic switch of a CTCF-flanked region of the Xist promoter determines the Xist transcription program

Tsix-mediated epigenetic switch of a CTCF-flanked region of the Xist promoter determines the Xist transcription program
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DOI:
10.1101/gad.389006
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发表时间:
2006-10-15
影响因子:
10.5
通讯作者:
Rougeulle, Claire
Rougeulle, Claire
中科院分区:
生物学1区
文献类型:
--
作者:
Navarro, Pablo;Page, Damian R.;Rougeulle, Claire

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启动X失活依赖于正义/反义对Xist/Tsix的协调表达。我们在这里表明,一个精确定义的Xist启动子区两侧CTCF是由Tsix在异染色质样状态在未分化的胚胎干细胞(ES)和转移到一个假常染色质结构Tsix截断。我们进一步证明,Xist 5'区域分化前的表观遗传状态预测了分化期间转录机器招募到Xist启动子的效率。我们的研究结果提供了机制的见解Tsix介导的表观遗传调控Xist导致Xist启动子激活和启动X失活分化ES细胞。
Initiation of X inactivation depends on the coordinated expression of the sense/antisense pair Xist/Tsix. We show here that a precisely defined Xist promoter region flanked by CTCF is maintained by Tsix in a heterochromatic-like state in undifferentiated embryonic stem (ES) cells and shifts to a pseudoeuchromatic structure upon Tsix truncation. We further demonstrate that the epigenetic state of the Xist 5' region prior to differentiation predicts the efficiency of transcriptional machinery recruitment to the Xist promoter during differentiation. Our results provide mechanistic insights into the Tsix-mediated epigenetic regulation of Xist resulting in Xist promoter activation and initiation of X inactivation in differentiating ES cells.