BioResource Center, RIKEN, 305-0024 Tsukuba, Japan.
Science. 2010 Oct 22;330(6003):496-9. doi: 10.1126/science.1194174. Epub 2010 Sep 16.
Cloning mammals by means of somatic cell nuclear transfer (SCNT) is highly inefficient because of erroneous reprogramming of the donor genome. Reprogramming errors appear to arise randomly, but the nature of nonrandom, SCNT-specific errors remains elusive. We found that Xist, a noncoding RNA that inactivates one of the two X chromosomes in females, was ectopically expressed from the active X (Xa) chromosome in cloned mouse embryos of both sexes. Deletion of Xist on Xa showed normal global gene expression and resulted in about an eight- to ninefold increase in cloning efficiency. We also identified an Xist-independent mechanism that specifically down-regulated a subset of X-linked genes through somatic-type repressive histone blocks. Thus, we have identified nonrandom reprogramming errors in mouse cloning that can be altered to improve the efficiency of SCNT methods.
通过体细胞核移植（SCNT）克隆哺乳动物的效率非常低，因为供体基因组的错误重编程。重编程错误似乎是随机发生的，但非随机的、SCNT 特异性错误的性质仍然难以捉摸。我们发现，Xist 是一种非编码 RNA，它使女性的两条 X 染色体中的一条失活，在雌雄克隆小鼠胚胎中从活性 X（Xa）染色体异位表达。Xa 上的 Xist 缺失显示出正常的全局基因表达，并导致克隆效率提高约八到九倍。我们还发现了一种不依赖 Xist 的机制，该机制通过体细胞核型抑制组蛋白块特异性地下调一组 X 连锁基因。因此，我们已经确定了在小鼠克隆中存在非随机的重编程错误，可以通过这些错误来提高 SCNT 方法的效率。
