Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Cold Spring Harb Perspect Biol. 2013 Aug 1;5(8):a010132. doi: 10.1101/cshperspect.a010132.
Patterns of replication within eukaryotic genomes correlate with gene expression, chromatin structure, and genome evolution. Recent advances in genome-scale mapping of replication kinetics have allowed these correlations to be explored in many species, cell types, and growth conditions, and these large data sets have allowed quantitative and computational analyses. One striking new correlation to emerge from these analyses is between replication timing and the three-dimensional structure of chromosomes. This correlation, which is significantly stronger than with any single histone modification or chromosome-binding protein, suggests that replication timing is controlled at the level of chromosomal domains. This conclusion dovetails with parallel work on the heterogeneity of origin firing and the competition between origins for limiting activators to suggest a model in which the stochastic probability of individual origin firing is modulated by chromosomal domain structure to produce patterns of replication. Whether these patterns have inherent biological functions or simply reflect higher-order genome structure is an open question.
真核基因组内的复制模式与基因表达、染色质结构和基因组进化相关。最近在全基因组范围内对复制动力学进行的图谱绘制，使得这些相关性可以在许多物种、细胞类型和生长条件下进行研究，并且这些大型数据集也允许进行定量和计算分析。这些分析中出现的一个引人注目的新相关性是复制时间与染色体三维结构之间的相关性。这种相关性与任何单一的组蛋白修饰或染色体结合蛋白都显著相关，表明复制时间是在染色体域的水平上进行控制的。这一结论与关于起始原点点火的异质性和起源原点之间对有限激活剂的竞争的平行工作相吻合，提出了一个模型，即单个起始原点点火的随机概率通过染色体域结构进行调节，从而产生复制模式。这些模式是否具有内在的生物学功能，还是仅仅反映了更高阶的基因组结构，这是一个悬而未决的问题。
