Tsix RNA and the germline factor, PRDM14, link X reactivation and stem cell reprogramming.
Tsix RNA and the germline factor, PRDM14, link X reactivation and stem cell reprogramming.
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TSIX RNA和种系因子PRDM14，链接X重新激活和干细胞再编程。
DOI：
10.1016/j.molcel.2013.10.023
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发表时间：
2013-12-26
期刊：
影响因子：
16
通讯作者：
Lee JT
中科院分区：
文献类型：
--
作者：
Payer B;Rosenberg M;Yamaji M;Yabuta Y;Koyanagi-Aoi M;Hayashi K;Yamanaka S;Saitou M;Lee JT
多能性和分化状态之间的转变以戏剧性的表观遗传变化为标志。细胞分化与X染色体失活（XCI）密切相关，而重编程为诱导多能干细胞（iPSC）与X染色体再激活（XCR）相关。XCR逆转无活性X的沉默状态，发生在小鼠胚泡和生殖细胞中。尽管它很重要，但人们对它的基本机制知之甚少。在这里，我们研究了长的非编码Tsix RNA和生殖系因子PRDM14的作用。在囊胚中，XCR受到Tsix或Prdm14突变的干扰。在iPSC中，XCR仅被PRDM14缺陷破坏，这也影响iPSC的衍生和维持。我们发现Tsix和PRDM14直接将XCR与多能性联系起来：首先，PRDM14通过招募Polycomb抑制复合物2来抑制Rnf12。其次，Tsix是PRDM14结合Xist所必需的。因此，我们的研究提供了细胞和X染色体重编程之间的功能和机制联系。
Transitions between pluripotent and differentiated states are marked by dramatic epigenetic changes. Cellular differentiation is tightly linked to X-chromosome inactivation (XCI), whereas reprogramming to induced pluripotent stem cells (iPSCs) is associated with X-chromosome reactivation (XCR). XCR reverses the silent state of the inactive X, occurring in vivo in mouse blastocysts and the germline. In spite of its importance, little is known about underlying mechanisms. Here, we examine the role of the long noncoding Tsix RNA and the germline factor, PRDM14. In blastocysts, XCR is perturbed by mutation of either Tsix or Prdm14. In iPSCs, XCR is disrupted only by PRDM14-deficiency, which also affects iPSC derivation and maintenance. We show that Tsix and PRDM14 directly link XCR to pluripotency: First, PRDM14 represses Rnf12 by recruiting Polycomb repressive complex 2. Second, Tsix is required for PRDM14 to bind Xist. Thus, our study provides functional and mechanistic links between cellular and X-chromosomal reprogramming.