Xist has properties of the X-chromosome inactivation centre
Xist has properties of the X-chromosome inactivation centre
复制标题
DOI：
10.1038/386272a0
复制
发表时间：
1997-03-20
期刊：
影响因子：
64.8
通讯作者：
Ashworth, A
中科院分区：
文献类型：
--
作者：
Herzing, LBK;Romer, JT;Ashworth, A
X染色体失活是雌性哺乳动物（具有两条X染色体）实现与雄性（一条X染色体和一条Y染色体）X染色体基因表达相当的过程(1,2)。这导致雌性体细胞中其中一条X染色体上几乎所有基因的转录沉默。X染色体失活已被证明是顺式作用的，并从X染色体上一个被称为X失活中心（Xic）的单一位置起始并扩散(2,3)。Xic已被定位在小鼠X染色体的一个450千碱基区域(4)。Xist基因也定位于该区域，并且仅从失活的X染色体表达(3 - 7)。Xist不同寻常之处在于它似乎不编码蛋白质，而是产生一种与失活的X染色体共定位的核RNA(4,8)。在胚胎干细胞中创建Xist的无效等位基因已经证明，该基因是顺式X失活发生所必需的(9)。在此我们表明，引入到常染色体上的Xist自身足以在顺式中导致失活，并且Xist RNA定位于靠近整合该基因的常染色体附近。此外，常染色体Xist拷贝的存在导致一些细胞中内源性Xist基因的激活，这表明染色体计数某些方面所需的元件包含在构建体中。因此，Xist基因表现出X失活中心的特性。
X-chromosome inactivation is the process by which female mammals (with two X chromosomes) achieve expression of X-chromosomal genes equivalent to that of males (one X and one Y chromosome)(1,2). This results in the transcriptional silencing of virtually all genes on one of the X chromosomes in female somatic cells, X-chromosome inactivation has been shown to act in cis and to initiate and spread from a single site on the X chromosome known as the X-inactivation centre (Xic)(2,3). The Xic has been localized to a 450-kilobase region of the mouse X chromosome(4). The Xist gene also maps to this region and is expressed exclusively from the inactive X chromosome(3-7). Xist is unusual in that it appears not to code for a protein but produces a nuclear RNA which colocalizes with the inactive X chromosome(4,8). The creation of a null allele of Xist in embryonic stem cells has demonstrated that this gene is required for X inactivation to occur in cis(9). Here we show that Xist, introduced onto an autosome, is sufficient by itself far inactivation in cis and that Xist RNA becomes localized close to the autosome into which the gene is integrated. In addition, the presence of autosomal Xist copies leads to activation of the endogeneous Xist gene in some cells, suggesting that elements required for some aspects of chromosome counting are contained within the construct, Thus the Xist gene exhibits properties of the X-inactivation centre.