Pourkarimi Ehsan, Bellush James M, Whitehouse Iestyn
Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, United States.
Elife. 2016 Dec 23;5:e21728. doi: 10.7554/eLife.21728.
The primary task of developing embryos is genome replication, yet how DNA replication is integrated with the profound cellular changes that occur through development is largely unknown. Using an approach to map DNA replication at high resolution in , we show that replication origins are marked with specific histone modifications that define gene enhancers. We demonstrate that the level of enhancer associated modifications scale with the efficiency at which the origin is utilized. By mapping replication origins at different developmental stages, we show that the positions and activity of origins is largely invariant through embryogenesis. Contrary to expectation, we find that replication origins are specified prior to the broad onset of zygotic transcription, yet when transcription initiates it does so in close proximity to the pre-defined replication origins. Transcription and DNA replication origins are correlated, but the association breaks down when embryonic cell division ceases. Collectively, our data indicate that replication origins are fundamental organizers and regulators of gene activity through embryonic development.
发育中胚胎的主要任务是基因组复制，然而DNA复制如何与发育过程中发生的深刻细胞变化整合在一起，在很大程度上仍是未知的。我们采用一种方法在高分辨率下绘制DNA复制图谱，结果表明复制起点带有特定的组蛋白修饰，这些修饰定义了基因增强子。我们证明，与增强子相关的修饰水平与复制起点的利用效率成比例。通过绘制不同发育阶段的复制起点图谱，我们发现复制起点的位置和活性在胚胎发生过程中基本不变。与预期相反，我们发现复制起点在合子转录广泛开始之前就已确定，然而当转录开始时，它是在紧邻预先定义的复制起点的位置进行的。转录和DNA复制起点是相关的，但当胚胎细胞分裂停止时，这种关联就会瓦解。总体而言，我们的数据表明，复制起点是胚胎发育过程中基因活性的基本组织者和调节者。
