Jaenisch R, Beard C, Lee J, Marahrens Y, Panning B
Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge 02142, USA.
Novartis Found Symp. 1998;214:200-9; discussion 209-13, 228-32. doi: 10.1002/9780470515501.ch12.
X chromosome inactivation in mammals requires expression of the gene Xist, which maps to the X chromosome inactivation centre (Xic) and encodes an untranslated RNA. Truncation of Xist RNA by gene targeting is lethal for female embryos and prevents the inactivation of the X chromosome carrying the deletion. This indicates that Xist RNA is necessary for initiation and propagation of the inactivation process. Xist is transcribed from the inactive X and its expression is silenced by DNA methylation, suggesting that methylation is crucial for shielding the active X chromosome against the inactivation process. Gene transfer experiments using transgenes the size of yeast artificial chromosomes have determined that a 450 kb fragment of DNA carrying Xist acts as an inactivation centre and is sufficient for initiation, propagation and maintenance of the inactive state. The elements for counting and choosing X chromosomes are part of the transgene. We have shown that X inactivation is mediated by a post-translational mechanism, i.e. the stabilization of Xist RNA, rather than by the regulation of the Xist promoter.
哺乳动物的X染色体失活需要Xist基因的表达，该基因定位于X染色体失活中心（Xic）并编码一种非翻译RNA。通过基因靶向截短Xist RNA对雌性胚胎是致死性的，并阻止携带缺失的X染色体失活。这表明Xist RNA对于失活过程的起始和传播是必需的。Xist从失活的X染色体转录而来，其表达通过DNA甲基化被沉默，这表明甲基化对于保护活性X染色体免受失活过程的影响至关重要。使用酵母人工染色体大小的转基因进行的基因转移实验已经确定，携带Xist的450 kb DNA片段作为失活中心，足以起始、传播和维持失活状态。计数和选择X染色体的元件是转基因的一部分。我们已经表明，X失活是由一种翻译后机制介导的，即Xist RNA的稳定化，而不是由Xist启动子的调控介导的。
