DNA复制在每个细胞周期的人类染色体上起始于约50,000个起始点，并假设这些起始点是由因子如起始识别复合物（ORC）或CTCF或其他特征如G-四链体的结合所指定的。我们对113个全基因组的人类起始点剖析（来自五种不同技术）及5个ORC结合位点数据集进行了综合分析，以批判性地评估最可重现的起始点是否由这些特征所指定。在所有数据集中报告的约7.5百万个300碱基对的染色体片段中，只有0.27%被四种技术可重复检测出（共20,250个共享的起始点），表明在不同情况下起始点的使用和鉴定存在广泛的变异。共享的起始点中有21%与转录启动子重叠，提出了一个难题。尽管共享的起始点与组成性CTCF结合位点、G-四链体位点和激活性组蛋白标记位点的重叠情况比联合起始点要多，但这些重叠情况与已知的转录起始位点相比，重叠情况是可比较的或更少的，因此这些特征可能因为起始点与表观遗传上开放的、类似启动子的序列相重叠而富集起来。在20,250个共享的起始点中，只有6.4%在人类癌细胞的约13,000个可重现ORC结合位点的1 kb范围内，与两者在酵母S. cerevisiae中的几乎100%重叠情况形成对比。因此，在人类癌细胞系中，复制起始点似乎是由高度可变的随机事件指定的，这种事件依赖于启动子周围的高表观遗传可及性，在最可重现的起始点与ORC结合位点之间没有广泛的重叠。

DNA replication initiates from ∼50,000 origins on human chromosomes in each cell-cycle and the origins are hypothesized to be specified by binding of factors like the Origin Recognition Complex (ORC) or CTCF or other features like G-quadruplexes. We have performed an integrative analysis of 113 genome-wide human origin profiles (from five different techniques) and 5 ORC-binding site datasets to critically evaluate whether the most reproducible origins are specified by these features. Out of ∼7.5 million 300 bp chromosomal fragments reported to harbor origins by all the datasets, only 0.27% were reproducibly detected by four techniques (20,250 shared origins), suggesting extensive variability in origin usage and identification in different circumstances. 21% of the shared origins overlap with transcriptional promoters, posing a conundrum. Although the shared origins overlap more than union origins with constitutive CTCF binding sites, G-quadruplex sites and activating histone marks, these overlaps are comparable or less than that of known Transcription Start Sites, so that these features could be enriched in origins because of the overlap of origins with epigenetically open, promoter-like sequences. Only 6.4% of the 20,250 shared origins were within 1 kb from any of the ∼13,000 reproducible ORC binding sites in human cancer cells, in contrast to the nearly 100% overlap between the two in the yeast, S. cerevisiae . Thus, in human cancer cell-lines, replication origins appear to be specified by highly variable stochastic events dependent on the high epigenetic accessibility around promoters, without extensive overlap between the most reproducible origins and ORC-binding sites.