Tata Institute of Fundamental Research, Centre for Interdisciplinary Sciences, Hyderabad 500046, India.
Nucleic Acids Res. 2021 Apr 6;49(6):3077-3091. doi: 10.1093/nar/gkab094.
The chromosome of Escherichia coli is riddled with multi-faceted complexity. The emergence of chromosome conformation capture techniques are providing newer ways to explore chromosome organization. Here we combine a beads-on-a-spring polymer-based framework with recently reported Hi-C data for E. coli chromosome, in rich growth condition, to develop a comprehensive model of its chromosome at 5 kb resolution. The investigation focuses on a range of diverse chromosome architectures of E. coli at various replication states corresponding to a collection of cells, individually present in different stages of cell cycle. The Hi-C data-integrated model captures the self-organization of E. coli chromosome into multiple macrodomains within a ring-like architecture. The model demonstrates that the position of oriC is dependent on architecture and replication state of chromosomes. The distance profiles extracted from the model reconcile fluorescence microscopy and DNA-recombination assay experiments. Investigations into writhe of the chromosome model reveal that it adopts helix-like conformation with no net chirality, earlier hypothesized in experiments. A genome-wide radius of gyration map captures multiple chromosomal interaction domains and identifies the precise locations of rrn operons in the chromosome. We show that a model devoid of Hi-C encoded information would fail to recapitulate most genomic features unique to E. coli.
大肠杆菌的染色体充满了多方面的复杂性。染色体构象捕获技术的出现为探索染色体组织提供了新的方法。在这里,我们结合基于弹簧珠的聚合物框架和最近报道的大肠杆菌染色体 Hi-C 数据,在丰富的生长条件下,开发了一个分辨率为 5kb 的综合模型。该研究集中于在不同复制状态下,对应于一组细胞,分别处于细胞周期的不同阶段的大肠杆菌的各种不同的染色体结构。Hi-C 数据集成模型捕获了大肠杆菌染色体在环状结构内自我组织成多个大域的过程。该模型表明 oriC 的位置取决于染色体的结构和复制状态。从模型中提取的距离分布与荧光显微镜和 DNA 重组实验结果相吻合。对染色体模型的扭曲的研究表明,它采用了没有净手性的螺旋状构象,这在实验中已经被假设。全基因组旋距图谱捕获了多个染色体相互作用域,并确定了染色体中 rrn 操纵子的确切位置。我们表明,一个没有 Hi-C 编码信息的模型将无法再现大肠杆菌特有的大多数基因组特征。