Impeding Xist Expression from the Active X Chromosome Improves Mouse Somatic Cell Nuclear Transfer
Impeding Xist Expression from the Active X Chromosome Improves Mouse Somatic Cell Nuclear Transfer
复制标题
DOI：
10.1126/science.1194174
复制
发表时间：
2010-10-22
期刊：
影响因子：
56.9
通讯作者：
Ogura, Atsuo
中科院分区：
文献类型：
--
作者：
Inoue, Kimiko;Kohda, Takashi;Ogura, Atsuo
通过体细胞核移植（SCNT）克隆哺乳动物是非常低效的，因为错误的重编程供体基因组。重编程错误似乎是随机出现的，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（一种使雌性两条X染色体中的一条失活的非编码RNA）在雌雄克隆小鼠胚胎中从活性X （Xa）染色体上异位表达。Xist在Xa上的缺失显示了正常的基因表达，克隆效率提高了8 - 9倍。我们还发现了一种不依赖于xist的机制，该机制通过躯体型抑制性组蛋白阻断特异性下调x连锁基因的子集。因此，我们已经确定了小鼠克隆中的非随机重编程错误，可以改变这些错误以提高SCNT方法的效率。
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.