Primary non-random X inactivation associated with disruption of Xist promoter regulation
Primary non-random X inactivation associated with disruption of Xist promoter regulation
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DOI：
10.1093/hmg/10.6.581
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发表时间：
2001-03-15
影响因子：
3.5
通讯作者：
Brockdorff, N
中科院分区：
文献类型：
--
作者：
Newall, AET;Duthie, S;Brockdorff, N
在这份报告中，我们证明了主要的非随机X染色体失活后，立即Xist启动子P-1的上游区域的靶向诱变。在杂合子动物中，在80-90%的细胞中存在靶向X染色体的优先失活。表型与一部分突变XY胚胎干细胞中Xist的不适当激活相关。链特异性分析显示增加的有义转录起始于Xist启动子P-1的上游。然而，从反义Tsix基因的转录没有明显的影响，我们证明，在体外和体内表型是特别归因于在靶位点的PGKneo盒的存在。这些研究结果进行了讨论的背景下，了解Xist基因调控X失活的机制。
In this report we demonstrate primary non-random X chromosome inactivation following targeted mutagenesis of a region immediately upstream of Xist promoter P-1. In heterozygous animals there is a preferential inactivation of the targeted X chromosome in 80-90% of cells, The phenotype correlates with inappropriate activation of Xist in a proportion of the mutant XY embryonic stem cells. Strand-specific analysis revealed increased sense transcription initiating upstream of Xist promoter P-1. There was, however, no discernible effect on transcription from the antisense Tsix gene, We demonstrate that the in vitro and in vivo phenotypes are specifically attributable to the presence of a PGKneo cassette at the targeted locus. These findings are discussed in the context of understanding mechanisms of Xist gene regulation in X inactivation.