The three-dimensional organization of the genome supports regulated gene expression, recombination, DNA repair, and chromosome segregation during mitosis. Chromosome conformation capture (Hi-C) 1 , 2 analysis has revealed a complex genomic landscape of internal chromosomal structures in vertebrate cells 3 – 7 , but the identical sequence of sister chromatids has made it difficult to determine how they topologically interact in replicated chromosomes. Here we describe sister-chromatid-sensitive Hi-C (scsHi-C), which is based on labelling of nascent DNA with 4-thio-thymidine and nucleoside conversion chemistry. Genome-wide conformation maps of human chromosomes reveal that sister-chromatid pairs interact most frequently at the boundaries of topologically associating domains (TADs). Continuous loading of a dynamic cohesin pool separates sister-chromatid pairs inside TADs and is required to focus sister-chromatid contacts at TAD boundaries. We identified a subset of TADs that are overall highly paired and are characterized by facultative heterochromatin and insulated topological domains that form separately within individual sister chromatids. The rich pattern of sister-chromatid topologies and our scsHi-C technology will make it possible to investigate how physical interactions between identical DNA molecules contribute to DNA repair, gene expression, chromosome segregation, and potentially other biological processes. Modified chromosome conformation capture (Hi-C) technology is used to characterize the interactions between sister chromatids, despite their identical DNA sequences.

中文翻译：

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复制的人类基因组中姐妹染色单体的构象


基因组的三维组织支持有丝分裂过程中受调控的基因表达、重组、DNA 修复和染色体分离。染色体构象捕获 (Hi-C) 1 , 2 分析揭示了脊椎动物细胞内部染色体结构的复杂基因组景观 3 – 7 ，但姐妹染色单体的相同序列使得很难确定它们在复制的染色体中如何拓扑相互作用。在这里，我们描述了姐妹染色单体敏感的 Hi-C (scsHi-C)，它基于用 4-硫代胸苷和核苷转换化学标记新生 DNA。人类染色体的全基因组构象图显示，姐妹染色单体对在拓扑关联域（TAD）的边界处相互作用最频繁。动态粘连蛋白池的连续加载可分离 TAD 内的姐妹染色单体对，并且需要将姐妹染色单体接触集中在 TAD 边界处。我们鉴定了 TAD 的一个子集，它们总体上高度配对，其特征是兼性异染色质和在各个姐妹染色单体内单独形成的绝缘拓扑结构域。姐妹染色单体拓扑的丰富模式和我们的 scsHi-C 技术将使得研究相同 DNA 分子之间的物理相互作用如何促进 DNA 修复、基因表达、染色体分离和潜在的其他生物过程成为可能。改良染色体构象捕获 (Hi-C) 技术用于表征姐妹染色单体之间的相互作用，尽管它们的 DNA 序列相同。