Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Cell. 2011 Jul 8;146(1):119-33. doi: 10.1016/j.cell.2011.06.026.
The long noncoding Xist RNA inactivates one X chromosome in the female mammal. Current models posit that Xist induces silencing as it spreads along X and recruits Polycomb complexes. However, the mechanisms for Xist loading and spreading are currently unknown. Here, we define the nucleation center for Xist RNA and show that YY1 docks Xist particles onto the X chromosome. YY1 is a "bivalent" protein, capable of binding both RNA and DNA through different sequence motifs. Xist's exclusive attachment to the inactive X is determined by an epigenetically regulated trio of YY1 sites as well as allelic origin. Specific YY1-to-RNA and YY1-to-DNA contacts are required to load Xist particles onto X. YY1 interacts with Xist RNA through Repeat C. We propose that YY1 acts as adaptor between regulatory RNA and chromatin targets.
长链非编码 RNA Xist 使雌性哺乳动物的一条 X 染色体失活。目前的模型假设 Xist 沿着 X 扩散并招募 Polycomb 复合物时诱导沉默。然而,Xist 的加载和扩散机制目前尚不清楚。在这里,我们定义了 Xist RNA 的成核中心,并表明 YY1 将 Xist 颗粒停靠在 X 染色体上。YY1 是一种“双价”蛋白,能够通过不同的序列基序结合 RNA 和 DNA。Xist 仅附着于失活 X 由一组受表观遗传调控的 YY1 位点以及等位基因来源决定。将 Xist 颗粒加载到 X 上需要特定的 YY1-to-RNA 和 YY1-to-DNA 接触。YY1 通过重复 C 与 Xist RNA 相互作用。我们提出 YY1 作为调节 RNA 和染色质靶标的衔接子。