在干細(xì)胞分化及X-染色體失活（使一個(gè)雌性X-染色體沉默,、以確保兩性之間基因劑量對(duì)等的過(guò)程）期間，染色質(zhì)發(fā)生表觀遺傳重新編程而鎖定在一個(gè)新?tīng)顟B(tài)。 將分化的細(xì)胞重新編程為“iPS細(xì)胞”還會(huì)使失活的X-染色體被重新激活,，而且曾有人提出,，多能因子Oct4聯(lián)系著這兩個(gè)過(guò)程,。
在這項(xiàng)研究中,，Donohue等人發(fā)現(xiàn),，Oct4通過(guò)觸發(fā)X染色體配對(duì)和計(jì)數(shù)來(lái)調(diào)控X-染色體失活。Oct4與非編碼RNA（Tsix 和 Xite）和蛋白（Ctcf 和Yy1）都發(fā)生相互作用,。這項(xiàng)工作表明,，干細(xì)胞中的X-染色體的表觀遺傳重新編程涉及一個(gè)復(fù)雜的網(wǎng)絡(luò)。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 460, 128-132 (2 July 2009) | doi:10.1038/nature08098
The pluripotency factor Oct4 interacts with Ctcf and also controls X-chromosome pairing and counting
Mary E. Donohoe1,2,3,5,6, Susana S. Silva1,2,3,5, Stefan F. Pinter1,2,3, Na Xu1,2,3 & Jeannie T. Lee1,2,3,4
1 Howard Hughes Medical Institute,
2 Department of Molecular Biology, Massachusetts General Hospital,
3 Department of Genetics, Harvard Medical School,
4 Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
5 These authors contributed equally to this work.
6 Present address: Burke Medical Research Institute, Weill Cornell Medical College, White Plains, New York 10605, USA.
Pluripotency of embryonic stem (ES) cells is controlled by defined transcription factors1, 2. During differentiation, mouse ES cells undergo global epigenetic reprogramming, as exemplified by X-chromosome inactivation (XCI) in which one female X chromosome is silenced to achieve gene dosage parity between the sexes3, 4, 5. Somatic XCI is regulated by homologous X-chromosome pairing6, 7 and counting8, 9, 10, and by the random choice of future active and inactive X chromosomes. XCI and cell differentiation are tightly coupled11, as blocking one process compromises the other8, 12 and dedifferentiation of somatic cells to induced pluripotent stem cells is accompanied by X chromosome reactivation2. Recent evidence suggests coupling of Xist expression to pluripotency factors occurs13, but how the two are interconnected remains unknown. Here we show that Oct4 (also known as Pou5f1)14 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 noncoding RNA genes of the X-inactivation centre15, 16, and also complexes with XCI trans-factors, Ctcf and Yy1 (ref. 17), through protein–protein interactions. Depletion of Oct4 blocks homologous X-chromosome pairing and results in the inactivation of both X chromosomes in female cells. Thus, we have identified the first trans-factor that regulates counting, and ascribed new functions to Oct4 during X-chromosome reprogramming.
