DNA replication initiates from multiple genomic locations called replication origins. In metazoa, DNA sequence elements involved in origin specification remain elusive. Here, we examine pluripotent, primary, differentiating, and immortalized human cells, and demonstrate that a class of origins, termed core origins, is shared by different cell types and host ~80% of all DNA replication initiation events in any cell population. We detect a shared G-rich DNA sequence signature that coincides with most core origins in both human and mouse genomes. Transcription and G-rich elements can independently associate with replication origin activity. Computational algorithms show that core origins can be predicted, based solely on DNA sequence patterns but not on consensus motifs. Our results demonstrate that, despite an attributed stochasticity, core origins are chosen from a limited pool of genomic regions. Immortalization through oncogenic gene expression, but not normal cellular differentiation, results in increased stochastic firing from heterochromatin and decreased origin density at TAD borders.

DNA 复制从称为复制起点的多个基因组位置开始。在后生动物中，涉及起源规范的 DNA 序列元素仍然难以捉摸。在这里，我们检查了多能、原代、分化和永生化的人类细胞，并证明了一类起源，称为核心起源，由不同细胞类型和宿主共享，占任何细胞群中所有 DNA 复制起始事件的 80%。我们检测到一个共享的富含 G 的 DNA 序列特征，该特征与人类和小鼠基因组中的大多数核心起源一致。转录和富含 G 的元素可以独立地与复制起点活动相关联。计算算法表明可以预测核心起源，仅基于 DNA 序列模式而不是共有基序。我们的结果表明，尽管归因于随机性，核心起源是从有限的基因组区域库中选择的。通过致癌基因表达永生化，但不是正常的细胞分化，导致异染色质的随机放电增加和 TAD 边界处的起源密度降低。