Migeon B R, Kazi E, Haisley-Royster C, Hu J, Reeves R, Call L, Lawler A, Moore C S, Morrison H, Jeppesen P
McKusick Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, 21287-3914, USA.
Genomics. 1999 Jul 15;59(2):113-21. doi: 10.1006/geno.1999.5861.
X chromosome inactivation is the means to downregulate the transcriptional output of X chromosomes in female mammals. Essential DNA from the murine X inactivation center (Xic) has been identified by introducing it into male embryonic stem (ES) cells. To identify the essential sequences on human X chromosomes, we transfected male mouse ES cells with a YAC transgene containing 480 kb of the putative human X inactivation center (XIC). Despite little DNA sequence conservation, the human transgene is recognized as a second Xic in these XY mouse cells and induces random inactivation in chimeric mice derived from these cells. Inactivation is extensive on the X chromosome, but more localized on chromosome 11 carrying the transgene, demonstrating that initial inactivation and spreading of inactivation signals along the chromosome are independent events. Our results show for the first time that the DNA included in the human XIC transgene is sufficient to initiate random X inactivation, even in cells of another species. Interspecies XIC trangenes should facilitate further investigation of this process in humans and other mammals.
X染色体失活是雌性哺乳动物下调X染色体转录输出的方式。通过将来自小鼠X染色体失活中心（Xic）的必需DNA导入雄性胚胎干细胞，已对其进行了鉴定。为了鉴定人类X染色体上的必需序列，我们用包含480 kb假定人类X染色体失活中心（XIC）的YAC转基因转染雄性小鼠胚胎干细胞。尽管DNA序列保守性很低，但该人类转基因在这些XY小鼠细胞中被识别为第二个Xic，并在源自这些细胞的嵌合小鼠中诱导随机失活。失活在X染色体上广泛存在，但在携带转基因的11号染色体上更局限，这表明失活信号沿染色体的初始失活和扩散是独立事件。我们的结果首次表明，人类XIC转基因中包含的DNA足以启动随机X染色体失活，即使在另一个物种的细胞中也是如此。种间XIC转基因应有助于对人类和其他哺乳动物这一过程的进一步研究。
