Reactivation of Dyen chromosome upon reprogramming leads to changes in the replication pattern and 5hmC accumulation
Reactivation of Dyen chromosome upon reprogramming leads to changes in the replication pattern and 5hmC accumulation
复制标题
DOI：
10.1007/s00412-013-0433-x
复制
发表时间：
2014-03-01
期刊：
影响因子：
1.6
通讯作者：
Kiselev, Sergey L.
中科院分区：
文献类型：
--
作者：
Bogomazova, Alexandra N.;Lagarkova, Maria A.;Kiselev, Sergey L.
一旦被设定，雌性体细胞中X染色体的不活跃状态在随后的细胞分裂过程中一直保持不变。X染色体的不活跃状态具有许多特征，包括复制迟缓。与小鼠的诱导多能干细胞(IPSCs)相比，人类女性IPSCs中的X染色体在体细胞重新编程到多能性状态后通常保持不活跃，尽管最近的研究表明X染色体可能重新激活。在这里，我们证明了，在重新编程期间，不活跃的X染色体从晚期复制切换到同步复制，恢复了以前沉默的基因的转录。这一过程伴随着一个新的表观遗传标记或DNA去甲基化途径的中间产物-5-羟甲基胞嘧啶(5hmC)在激活的X染色体上的积累。我们的结果表明，早期复制和5hmC的重现能更好地证实X染色体的活性状态，而不是出现活性染色质的组蛋白标记，去除非活性染色质的组蛋白标记，或没有XIST涂层。
Once set, the inactive status of the X chromosome in female somatic cells is preserved throughout subsequent cell divisions. The inactive status of the X chromosome is characterized by many features, including late replication. In contrast to induced pluripotent stem cells (iPSCs) in mice, the X chromosome in human female iPSCs usually remains inactive after reprogramming of somatic cells to the pluripotent state, although recent studies point to the possibility of reactivation of the X chromosome. Here, we demonstrated that, during reprogramming, the inactive X chromosome switches from late to synchronous replication, with restoration of the transcription of previously silenced genes. This process is accompanied by accumulation of a new epigenetic mark or intermediate of the DNA demethylation pathway, 5-hydroxymethylcytosine (5hmC), on the activated X chromosome. Our results indicate that the active status of the X chromosome is better confirmed by early replication and the reappearance of 5hmC, rather than by appearance of histone marks of active chromatin, removal of histone marks of inactive chromatin, or an absence of XIST coating.