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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Sequencing newly replicated DNA reveals widespread plasticity in human replication timing
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Sequencing newly replicated DNA reveals widespread plasticity in human replication timing

机译：测序新复制的DNA揭示了人类复制时间的广泛可塑性

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摘要

Faithful transmission of genetic material to daughter cells involves a characteristic temporal order of DNA replication, which may play a significant role in the inheritance of epigenetic states. We developed a genome-scale approach-Repli Seq-to map temporally ordered replicating DNA using massively parallel sequencing and applied it to study regional variation in human DNA replication time across multiple human cell types. The method requires as few as 8,000 cytometry-fractionated cells for a single analysis, and provides high-resolution DNA replication patterns with respect to both cell-cycle time and ge-nomic position. We find that different cell types exhibit characteristic replication signatures that reveal striking plasticity in regional replication time patterns covering at least 50% of the human genome. We also identified autosomal regions with marked biphasic replication timing that include known regions of monoallelic expression as well as many previously uncharacterized domains. Comparison with high-resolution genome-wide profiles of DNasel sensitivity revealed that DNA replication typically initiates within foci of accessible chromatin comprising clustered DNasel hypersensitive sites, and that replication time is better correlated with chromatin accessibility than with gene expression. The data collectively provide a unique, genome-wide picture of the epigenetic compartmentalization of the human genome and suggest that cell-lineage specification involves extensive reprogramming of replication timing patterns.
机译：遗传物质向子细胞的忠实传播涉及DNA复制的特征性时间顺序，这可能在表观遗传状态的遗传中起重要作用。我们开发了一种基因组规模的方法-复制序列-使用大规模平行测序来映射时间有序的复制DNA，并将其应用于研究多种人类细胞中人类DNA复制时间的区域差异。该方法仅需进行一次细胞分析就可分离多达8,000个细胞，并提供有关细胞周期时间和基因组位置的高分辨率DNA复制模式。我们发现不同的细胞类型表现出特征性的复制特征，这些特征显示出覆盖至少50％的人类基因组的区域复制时间模式具有惊人的可塑性。我们还确定了具有明显的双相复制时机的常染色体区域，包括单等位基因表达的已知区域以及许多以前未表征的结构域。与DNasel敏感​​性的高分辨率全基因组图谱的比较表明，DNA复制通常在包含成簇的DNasel超敏性位点的可及染色质灶内开始，并且复制时间与染色质可及性比与基因表达更好地相关。这些数据共同提供了人类基因组表观遗传区隔的独特的全基因组图片，并表明细胞谱系规范涉及复制时序模式的大量重编程。

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  • 作者

    R. Scott Hansen; Sean Thomas; Richard Sandstrom; Theresa K. Canfield; Robert E. Thurman; Molly Weaver; Michael O. Dorschner; Stanley M. Gartler; John A. Stamatoyannopoulos;

  • 作者单位

    Department of Medicine, Division of Medical Genetics, and University of Washington School of Medicine, Seattle, WA 98195;

    Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195;

    Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195;

    Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195;

    Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195;

    Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195;

    Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195;

    Department of Medicine, Division of Medical Genetics, and University of Washington School of Medicine, Seattle, WA 98195 Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195;

    Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    chromatin structure; gene expression; tissue specificity;

    机译：染色质结构基因表达;组织特异性;

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