Journal
GENOME RESEARCH
Volume 17, Issue 6, Pages 865-876Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.5427007
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Funding
- NCI NIH HHS [R01 CA060499, R01 CA060499-14] Funding Source: Medline
- NHGRI NIH HHS [U01 HG003157, U01 HG003157-02, U01 HG003157-03, HG003157] Funding Source: Medline
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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.
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