Pan-S replication patterns and chromosomal domains defined by genome-tiling arrays of ENCODE genomic areas
Pan-S replication patterns and chromosomal domains defined by genome-tiling arrays of ENCODE genomic areas
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DOI：
10.1101/gr.5427007
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发表时间：
2007-06-01
期刊：
影响因子：
7
通讯作者：
Dutta, Anindya
中科院分区：
文献类型：
--
作者：
Karnani, Neerja;Taylor, Christopher;Dutta, Anindya
在真核生物中，准确控制复制时间是有效完成S阶段和保持基因组稳定性的关键。我们提出了一种基于高分辨率基因组拼接阵列的复制时间配置文件，其复制时间与ENCODE项目联盟研究的人类基因组的1%相似。被调查的片段中有20%是异步复制的(潘-S)。这些区域富含基因和CpG岛，这些都是它们与早期复制基因座共有的特征。间期FISH显示，潘-S的复制是复制时间等位基因间变异的结果，而不是源于特定的细胞周期同步方法或非整倍体。复制时间的等位基因间差异可能是由于染色质环境中的等位基因间差异造成的，因为当早复制区或晚复制区分别仅富含激活或抑制组蛋白修饰时，潘-S区域具有这两种类型的组蛋白修饰。染色体的复制图谱确定了数百个千碱基的连续染色体片段，这些片段被较小的片段隔开，在这些片段中，复制时间经历了急剧的转变。对其中一个片段的仔细研究表明，复制时间的延迟伴随着基因表达水平的下降和抑制性染色质标记的出现，表明过渡片段是分隔具有不同染色质环境的染色体结构域的边界元件。
In eukaryotes, accurate control of replication time is required for the efficient completion of S phase and maintenance of genome stability. We present a high-resolution genome-tiling array-based profile of replication timing for similar to 1% of the human genome studied by The ENCODE Project Consortium. Twenty percent of the investigated segments replicate asynchronously (pan-S). These areas are rich in genes and CpG islands, features they share with early-replicating loci. Interphase FISH showed that pan-S replication is a consequence of interallelic variation in replication time and is not an artifact derived from a specific cell cycle synchronization method or from aneuploidy. The interallelic variation in replication time is likely due to interallelic variation in chromatin environment, because while the early- or late-replicating areas were exclusively enriched in activating or repressing histone modifications, respectively, the pan-S areas had both types of histone modification. The replication profile of the chromosomes identified contiguous chromosomal segments of hundreds of kilobases separated by smaller segments where the replication time underwent an acute transition. Close examination of one such segment demonstrated that the delay of replication time was accompanied by a decrease in level of gene expression and appearance of repressive chromatin marks, suggesting that the transition segments are boundary elements separating chromosomal domains with different chromatin environments.