DNA replication timing during development anticipates transcriptional programs and parallels enhancer activation.
DNA replication timing during development anticipates transcriptional programs and parallels enhancer activation.
复制标题
发育过程中的 DNA 复制时间预测转录程序并与增强子激活平行。
DOI：
10.1101/gr.218602.116
复制
发表时间：
2017
期刊：
影响因子：
7
通讯作者：
Sansam,ChristopherL
中科院分区：
文献类型：
--
作者：
Siefert,JosephC;Georgescu,Constantin;Wren,JonathanD;Koren,Amnon;Sansam,ChristopherL
在分裂细胞中，DNA 复制以精确的顺序发生，但关于复制时间建立和调节的机制仍然存在许多问题。我们现在已经在斑马鱼发育过程中生成了全基因组、高分辨率的复制时序图。出乎意料的是，在囊胚转变之前的快速细胞周期中，存在一个明确的计时程序，可以预测合子转录的初始波。此后，复制时间在大部分基因组中逐步、持续地重塑，增强子激活涉及的表观遗传变化经常与复制时间的发育变化平行。 4 号染色体的长臂在原肠胚形成过程中经历了戏剧性的发育调节性转变，转向晚期复制，让人想起哺乳动物 X 染色体失活。这项研究表明，复制时间是动态的，并且与斑马鱼早期发育过程中的表观遗传和转录变化密切相关。这些数据提供了对复制时间的调节和功能的深入了解，并将有助于进一步的机制研究。
In dividing cells, DNA replication occurs in a precise order, but many questions remain regarding the mechanisms of replication timing establishment and regulation. We now have generated genome-wide, high-resolution replication timing maps throughout zebrafish development. Unexpectedly, in the rapid cell cycles preceding the midblastula transition, a defined timing program was present that predicted the initial wave of zygotic transcription. Replication timing was thereafter progressively and continuously remodeled across the majority of the genome, and epigenetic changes involved in enhancer activation frequently paralleled developmental changes in replication timing. The long arm of Chromosome 4 underwent a dramatic developmentally regulated switch to late replication during gastrulation, reminiscent of mammalian X Chromosome inactivation. This study reveals that replication timing is dynamic and tightly linked to epigenetic and transcriptional changes throughout early zebrafish development. These data provide insight into the regulation and functions of replication timing and will enable further mechanistic studies.