The pluripotency factor Oct4 interacts with Ctcf and also controls X-chromosome pairing and counting.
The pluripotency factor Oct4 interacts with Ctcf and also controls X-chromosome pairing and counting.
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DOI：
10.1038/nature08098
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发表时间：
2009-07-02
期刊：
影响因子：
64.8
通讯作者：
Lee, Jeannie T.
中科院分区：
文献类型：
--
作者：
Donohoe, Mary E.;Silva, Susana S.;Pinter, Stefan F.;Xu, Na;Lee, Jeannie T.
胚胎干细胞（ES）的多能性由特定的转录因子控制。在分化过程中，小鼠ES细胞经历全局表观遗传重编程，如X染色体失活（XCI）所示，其中一个雌性X染色体被沉默以实现性别之间的基因剂量均等。体细胞XCI受同源X染色体配对、计数和未来活性X（Xa）和非活性X的随机选择的调节。XCI和细胞分化是紧密耦合的，因为阻断一个过程会损害另一个过程，体细胞去分化为诱导多能干细胞（iPS）伴随着X-再活化。最近的证据表明Xist表达与多能性因子偶联，但两者如何相互关联仍不清楚。在这里，我们发现Oct 4位于XCI层次的顶部，并通过触发X染色体配对和计数来调节XCI。Oct 4直接结合X失活中心的两个调控ncRNA基因Tsix和Xite，并且还通过蛋白质-蛋白质相互作用与XCI反式因子Ctcf和Yy 1复合。Oct 4的缺失阻断了同源X染色体配对，并导致雌性细胞中两个X的失活。因此，我们已经确定了第一个调节计数的反式因子，并将X染色体重编程过程中的新功能归因于Oct 4。
Pluripotency of embryonic stem (ES) cells is controlled by defined transcription factors. During differentiation, mouse ES cells undergo global epigenetic reprogramming, as exemplified by X-chromosome inactivation (XCI) whereby one female X-chromosome is silenced to achieve gene dosage parity between the sexes. Somatic XCI is regulated by homologous X-chromosome pairing, counting, and random choice of future active X (Xa) and inactive X’s. XCI and cell differentiation are tightly coupled, as blocking one process compromises the other and dedifferentiation of somatic cells to induced pluripotent stem (iPS) cells is accompanied by X-reactivation. Recent evidence suggests coupling of Xist expression to pluripotency factors, but how the two are interconnected remains unknown. Here, we show that the Oct4 lies at the top of the XCI hierarchy and regulates XCI by triggering X-chromosome pairing and counting. Oct4 directly binds Tsix and Xite, two regulatory ncRNA genes of the X-inactivation center, and also complexes with XCI trans-factors, Ctcf and Yy1, through protein-protein interactions. Depletion of Oct4 blocks homologous X-chromosome pairing and results in inactivation of both Xs in female cells. Thus, we have identified the first trans-factor that regulates counting and ascribed novel functions to Oct4 during X-chromosome reprogramming.
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影响因子：
56.9
作者：
Xu, N;Tsai, CL;Lee, JT
通讯作者：
Lee, JT
影响因子：
11.4
作者：
Morey, C;Navarro, P;Clerc, P
通讯作者：
Clerc, P
影响因子：
64.5
作者：
Takahashi, Kazutoshi;Yamanaka, Shinya
通讯作者：
Yamanaka, Shinya
影响因子：
14.8
作者：
Lee, Tong Ihn;Johnstone, Sarah E.;Young, Richard A.
通讯作者：
Young, Richard A.
DOI：
10.1073/pnas.0712136105
发表时间：
2008-03-25
影响因子：
11.1
作者：
Silva, Susana S.;Rowntree, Rebecca K.;Lee, Jeannie T.
通讯作者：
Lee, Jeannie T.