Wutz Anton, Rasmussen Theodore P, Jaenisch Rudolf
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, USA.
Nat Genet. 2002 Feb;30(2):167-74. doi: 10.1038/ng820. Epub 2002 Jan 7.
The gene Xist initiates the chromosomal silencing process of X inactivation in mammals. Its product, a noncoding RNA, is expressed from and specifically associates with the inactive X chromosome in female cells. Here we use an inducible Xist expression system in mouse embryonic stem cells that recapitulates long-range chromosomal silencing to elucidate which Xist RNA sequences are necessary for chromosomal association and silencing. We show that chromosomal association and spreading of Xist RNA can be functionally separated from silencing by specific mutations. Silencing requires a conserved repeat sequence located at the 5' end of Xist. Deletion of this element results in Xist RNA that still associates with chromatin and spreads over the chromosome but does not effect transcriptional repression. Association of Xist RNA with chromatin is mediated by functionally redundant sequences that act cooperatively and are dispersed throughout the remainder of Xist but show little or no homology.
基因Xist启动了哺乳动物X染色体失活的染色体沉默过程。其产物是一种非编码RNA，由雌性细胞中的失活X染色体表达并与之特异性结合。在这里，我们在小鼠胚胎干细胞中使用了一种可诱导的Xist表达系统，该系统重现了长距离染色体沉默，以阐明哪些Xist RNA序列对于染色体结合和沉默是必需的。我们表明，Xist RNA的染色体结合和扩散在功能上可以通过特定突变与沉默分开。沉默需要位于Xist 5'端的保守重复序列。删除该元件会导致Xist RNA仍然与染色质结合并在染色体上扩散，但不会影响转录抑制。Xist RNA与染色质的结合由功能冗余序列介导，这些序列协同作用并分散在Xist的其余部分，但几乎没有同源性。
