Wellcome Trust and MRC Stem Cell Institute, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, UK.
Cell Mol Life Sci. 2013 Jul;70(14):2443-61. doi: 10.1007/s00018-012-1174-3. Epub 2012 Sep 30.
In mammals, one of the two X chromosomes of female cells is inactivated for dosage compensation between the sexes. X chromosome inactivation is initiated in early embryos by the noncoding Xist RNA. Subsequent chromatin modifications on the inactive X chromosome (Xi) lead to a remarkable stability of gene repression in somatic cell lineages. In mice, reactivation of genes on the Xi accompanies the establishment of pluripotent cells of the female blastocyst and the development of primordial germ cells. Xi reactivation also occurs when pluripotency is established during the reprogramming of somatic cells to induced pluripotent stem cells. The mechanism of Xi reactivation has attracted increasing interest for studying changes in epigenetic patterns and for improving methods of cell reprogramming. Here, we review recent advances in the understanding of Xi reactivation during development and reprogramming and illustrate potential clinical applications.
在哺乳动物中，雌性细胞的两条 X 染色体中的一条为了性别间的剂量补偿而失活。X 染色体失活由非编码的 Xist RNA 在早期胚胎中启动。随后，失活 X 染色体（Xi）上的染色质修饰导致体细胞谱系中基因抑制的显著稳定性。在小鼠中，Xi 上基因的重新激活伴随着雌性胚泡多能性细胞的建立和原始生殖细胞的发育。当体细胞重编程为诱导多能干细胞时，多能性建立也会发生 Xi 重新激活。Xi 重新激活的机制引起了人们越来越多的兴趣，以研究表观遗传模式的变化，并改进细胞重编程的方法。在这里，我们综述了在发育和重编程过程中对 Xi 重新激活的理解方面的最新进展，并说明了潜在的临床应用。
