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Single-cell Hi-C reveals cell-to-cell variability in chromosome structure

机译:单细胞Hi-C揭示了染色体结构中的细胞间差异

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摘要

Large-scale chromosome structure and spatial nuclear arrangement have been linked to control of gene expression and DNA replication and repair. Genomic techniques based on chromosome conformation capture (3C) assess contacts for millions of loci simultaneously, but do so by averaging chromosome conformations from millions of nuclei. Here we introduce single-cell Hi-C, combined with genome-wide statistical analysis and structural modelling of single-copy X chromosomes, to show that individual chromosomes maintain domain organization at the megabase scale, but show variable cell-to-cell chromosome structures at larger scales. Despite this structural stochasticity, localization of active gene domains to boundaries of chromosome territories is a hallmark of chromosomal conformation. Single-cell Hi-C data bridge current gaps between genomics and microscopy studies of chromosomes, demonstrating how modular organization underlies dynamic chromosome structure, and how this structure is probabilistically linked with genome activity patterns.
机译:大规模的染色体结构和空间核排列已与控制基因表达以及DNA复制和修复联系在一起。基于染色体构象捕获(3C)的基因组技术可以同时评估数百万个基因座的接触,但是可以通过平均数百万个核的染色体构象来进行评估。在这里,我们介绍单细胞Hi-C,并结合全基因组统计分析和单拷贝X染色体的结构建模,以显示单个染色体在megabase尺度上保持域组织,但显示可变的细胞间染色体结构更大的规模。尽管具有这种结构上的随机性,但将活性基因结构域定位在染色体区域的边界是染色体构象的标志。单细胞Hi-C数据弥补了基因组学和染色体显微镜研究之间的空白,证明了模块化组织如何构成动态染色体结构的基础,以及该结构如何与基因组活动模式概率关联。

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  • 来源
    《Nature》 |2013年第7469期|59-64|共6页
  • 作者单位

    Nuclear Dynamics Programme, The Babraham Institute, Cambridge CB22 3AT, UK;

    Department of Computer Science and Applied Mathematics and Department of Biological Regulation, Weizmann Institute, Rehovot 76100, Israel;

    Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK;

    Nuclear Dynamics Programme, The Babraham Institute, Cambridge CB22 3AT, UK;

    Department of Computer Science and Applied Mathematics and Department of Biological Regulation, Weizmann Institute, Rehovot 76100, Israel;

    Epigenetics Programme, The Babraham Institute, Cambridge CB22 3AT, UK;

    Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK;

    Department of Computer Science and Applied Mathematics and Department of Biological Regulation, Weizmann Institute, Rehovot 76100, Israel;

    Nuclear Dynamics Programme, The Babraham Institute, Cambridge CB22 3AT, UK;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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