Xu Na, Donohoe Mary E, Silva Susana S, Lee Jeannie T
Howard Hughes Medical Institute Department of Molecular Biology, Massachusetts General Hospital Department of Genetics, Harvard Medical School Boston, Massachusetts 02114, USA.
Nat Genet. 2007 Nov;39(11):1390-6. doi: 10.1038/ng.2007.5. Epub 2007 Oct 21.
X-chromosome inactivation (XCI) ensures the equality of X-chromosome dosages in male and female mammals by silencing one X in the female. To achieve the mutually exclusive designation of active X (Xa) and inactive X (Xi), the process necessitates that two Xs communicate in trans through homologous pairing. Pairing depends on a 15-kb region within the genes Tsix and Xite. Here, we dissect molecular requirements and find that pairing can be recapitulated by 1- to 2-kb subfragments of Tsix or Xite with little sequence similarity. However, a common denominator among them is the presence of the protein Ctcf, a chromatin insulator that we find to be essential for pairing. By contrast, the Ctcf-interacting partner, Yy1 (ref. 8), is not required. Pairing also depends on transcription. Transcriptional inhibition prevents new pair formation but does not perturb existing pairs. The kinetics suggest a pairing half-life of <1 h. We propose that pairing requires Ctcf binding and co-transcriptional activity of Tsix and Xite.
X染色体失活（XCI）通过使雌性中的一条X染色体沉默来确保雄性和雌性哺乳动物中X染色体剂量的平等。为了实现活性X（Xa）和失活X（Xi）的相互排斥指定，该过程需要两条X染色体通过同源配对进行反式交流。配对取决于基因Tsix和Xite内的一个15千碱基区域。在这里，我们剖析了分子要求，发现Tsix或Xite的1至2千碱基亚片段可以重现配对，且序列相似性很小。然而，它们之间的一个共同特征是蛋白质Ctcf的存在，我们发现Ctcf是一种染色质绝缘子，对配对至关重要。相比之下，不需要Ctcf相互作用伴侣Yy1（参考文献8）。配对也依赖于转录。转录抑制会阻止新的配对形成，但不会干扰现有的配对。动力学表明配对的半衰期小于1小时。我们提出，配对需要Ctcf结合以及Tsix和Xite的共转录活性。
