多能性因子结合和 Tsix 表达协同作用，抑制未分化胚胎干细胞中的 Xist。
Pluripotency factor binding and Tsix expression act synergistically to repress Xist in undifferentiated embryonic stem cells.
机构信息
Developmental Epigenetics Group, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
出版信息
Epigenetics Chromatin. 2011 Oct 7;4(1):17. doi: 10.1186/1756-8935-4-17.
BACKGROUND
Expression of Xist, the master regulator of X chromosome inactivation, is extinguished in pluripotent cells, a process that has been linked to programmed X chromosome reactivation. The key pluripotency transcription factors Nanog, Oct4 and Sox2 are implicated in Xist gene extinction, at least in part through binding to an element located in Xist intron 1. Other pathways, notably repression by the antisense RNA Tsix, may also be involved.
RESULTS
Here we employ a transgene strategy to test the role of the intron 1 element and Tsix in repressing Xist in ES cells. We find that deletion of the intron 1 element causes a small increase in Xist expression and that simultaneous deletion of the antisense regulator Tsix enhances this effect.
CONCLUSION
We conclude that Tsix and pluripotency factors act synergistically to repress Xist in undifferentiated embryonic stem cells. Double mutants do not exhibit maximal levels of Xist expression, indicating that other pathways also play a role.
背景
X 染色体失活的主调控因子 Xist 的表达在多能细胞中被熄灭，这个过程与程序性 X 染色体重新激活有关。关键的多能性转录因子 Nanog、Oct4 和 Sox2 被认为参与了 Xist 基因的熄灭，至少部分是通过与位于 Xist 内含子 1 中的一个元件结合来实现的。其他途径，特别是反义 RNA Tsix 的抑制作用，也可能参与其中。
结果
在这里，我们采用转基因策略来测试内含子 1 元件和 Tsix 在抑制 ES 细胞中 Xist 表达中的作用。我们发现，删除内含子 1 元件会导致 Xist 表达的小幅度增加，而同时删除反义调节剂 Tsix 会增强这种效应。
结论
我们得出结论，Tsix 和多能性因子协同作用，在未分化的胚胎干细胞中抑制 Xist 的表达。双突变体并不表现出 Xist 表达的最大水平，这表明其他途径也发挥了作用。
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