Department of Biological Science, Florida State University, Tallahassee, FL 32306-4295, USA.
San Diego Biomedical Research Institute, 3525 John Hopkins Court, San Diego, CA 92121, USA.
Curr Opin Genet Dev. 2023 Apr;79:102031. doi: 10.1016/j.gde.2023.102031. Epub 2023 Mar 9.
Decades of work on the spatiotemporal organization of mammalian DNA replication timing (RT) continues to unveil novel correlations with aspects of transcription and chromatin organization but, until recently, mechanisms regulating RT and the biological significance of the RT program had been indistinct. We now know that the RT program is both influenced by and necessary to maintain chromatin structure, forming an epigenetic positive feedback loop. Moreover, the discovery of specific cis-acting elements regulating mammalian RT at both the domain and the whole-chromosome level has revealed multiple cell-type-specific and developmentally regulated mechanisms of RT control. We review recent evidence for diverse mechanisms employed by different cell types to regulate their RT programs and the biological significance of RT regulation during development.
几十年来，人们一直在研究哺乳动物 DNA 复制时间（RT）的时空组织，不断揭示出与转录和染色质组织的各个方面的新关联，但直到最近，调节 RT 的机制以及 RT 程序的生物学意义仍然不清楚。我们现在知道，RT 程序既受染色质结构的影响，又对其有维持作用，形成一个表观遗传的正反馈循环。此外，在域和整条染色体水平上发现了调控哺乳动物 RT 的特定顺式作用元件，揭示了 RT 调控的多种细胞类型特异性和发育调控机制。我们综述了最近的证据，证明不同细胞类型采用不同的机制来调节它们的 RT 程序，以及在发育过程中 RT 调节的生物学意义。
