The Hadassah Human Embryonic Stem Cells Research Center, Goldyne-Savad Institute of Gene Therapy, Department of OB & GYN, Hadassah University Hospital, Jerusalem 91120, Israel.
Stem Cells. 2010 Mar 31;28(3):443-9. doi: 10.1002/stem.303.
Replication timing is an important developmentally regulated regional property that is correlated with chromosome structure and gene expression, but little is known about the establishment and maintenance of these patterns. Here we followed the fate of replication timing patterns in cells that undergo reprogramming either through somatic-cell nuclear transplantation or by the generation of induced pluripotential stem cells. We have investigated three different paradigms, stage-specific replication timing, parental allele-specific asynchrony (imprinted regions), and random allelic asynchronous replication. In all cases, somatic replication timing patterns were reset exactly at the appropriate stage in early development and could be properly established upon re-differentiation. Taken together, these results suggest that, unlike DNA methylation, the molecular mechanisms governing replication timing are not only stable but can also be easily reprogrammed.
复制时间是一个与染色体结构和基因表达相关的重要的发育调控的区域属性，但关于这些模式的建立和维持知之甚少。在这里，我们通过体细胞核移植或诱导多能干细胞的产生，研究了经历重编程的细胞中复制时间模式的命运。我们已经研究了三种不同的范例，即阶段特异性复制时间、亲本等位基因特异性异步（印迹区域）和随机等位基因异步复制。在所有情况下，体细胞复制时间模式在早期发育的适当阶段被完全重置，并且在重新分化时可以正确建立。总之，这些结果表明，与 DNA 甲基化不同，控制复制时间的分子机制不仅稳定，而且可以很容易地重新编程。
