Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
Genome Res. 2017 Aug;27(8):1406-1416. doi: 10.1101/gr.218602.116. Epub 2017 May 16.
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.
在细胞分裂过程中，DNA 复制按精确的顺序进行，但关于复制时间建立和调控的机制仍有许多问题尚未解决。我们现在已经生成了斑马鱼发育过程中全基因组的高分辨率复制时间图谱。出乎意料的是，在中胚层转换之前的快速细胞周期中，存在一个明确的时间程序，该程序预测了合子转录的初始波。此后，复制时间在基因组的大部分区域逐渐且连续地重塑，并且涉及增强子激活的表观遗传变化经常与复制时间的发育变化平行。染色体 4 的长臂在原肠胚形成过程中经历了戏剧性的发育调控开关，转变为晚期复制，类似于哺乳动物 X 染色体失活。这项研究揭示了复制时间在整个早期斑马鱼发育过程中是动态的，并与表观遗传和转录变化紧密相关。这些数据为复制时间的调控和功能提供了深入的了解，并将能够进一步进行机制研究。
