Howard Hughes Medical Institute, Department of Molecular Biology, Massachusetts General Hospital, Department of Genetics, Harvard Medical School, Boston, Massachusetts 02114, USA.
Genetics. 2011 Oct;189(2):441-54. doi: 10.1534/genetics.111.132662. Epub 2011 Aug 11.
In mammals, X-chromosome inactivation (XCI) equalizes X-linked gene expression between XY males and XX females and is controlled by a specialized region known as the X-inactivation center (Xic). The Xic harbors two chromatin interaction domains, one centered around the noncoding Xist gene and the other around the antisense Tsix counterpart. Previous work demonstrated the existence of a chromatin transitional zone between the two domains. Here, we investigate the region and discover a conserved element, RS14, that presents a strong binding site for Ctcf protein. RS14 possesses an insulatory function suggestive of a boundary element and is crucial for cell differentiation and growth. Knocking out RS14 results in compromised Xist induction and aberrant XCI in female cells. These data demonstrate that a junction element between Tsix and Xist contributes to the initiation of XCI.
在哺乳动物中,X 染色体失活(XCI)使 XY 雄性和 XX 雌性之间的 X 连锁基因表达达到平衡,并且受到一个称为 X 失活中心(Xic)的专门区域控制。Xic 含有两个染色质相互作用域,一个围绕非编码 Xist 基因,另一个围绕反义 Tsix 对应物。以前的工作表明,这两个域之间存在一个染色质过渡区。在这里,我们研究了这个区域,发现了一个保守的元素 RS14,它为 Ctcf 蛋白提供了一个很强的结合位点。RS14 具有一个隔离子的功能,暗示它是一个边界元件,对于细胞分化和生长至关重要。敲除 RS14 会导致 Xist 诱导受损和雌性细胞中的异常 XCI。这些数据表明,Tsix 和 Xist 之间的连接元件有助于 XCI 的启动。