Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome
Comprehensive Mapping of Long-Range Interactions Reveals Folding Principles of the Human Genome
复制标题
DOI：
10.1126/science.1181369
复制
发表时间：
2009-10-09
期刊：
影响因子：
56.9
通讯作者：
Dekker, Job
中科院分区：
文献类型：
--
作者：
Lieberman-Aiden, Erez;van Berkum, Nynke L.;Dekker, Job
我们描述了Hi-C，这是一种通过将基于邻近的连接与大规模并行测序相结合来探索整个基因组的三维结构的方法。我们用Hi-C构建了人类基因组的空间邻近图，分辨率为1兆。这些图谱证实了染色体区域的存在和小的、富含基因的染色体的空间接近。我们确定了基因组组织的另一个水平，其特征是开放和闭合染色质的空间分离形成了两个全基因组范围的间隔室。在兆基尺度上，染色质构象与分形球一致，分形球是一种无结的聚合物构象，能够最大限度地致密堆积，同时保持轻松折叠和展开任何基因组位点的能力。分形球体有别于更常用的球体平衡模型。我们的结果证明了Hi-C在绘制整个基因组的动态构象方面的能力。
We describe Hi-C, a method that probes the three-dimensional architecture of whole genomes by coupling proximity-based ligation with massively parallel sequencing. We constructed spatial proximity maps of the human genome with Hi-C at a resolution of 1 megabase. These maps confirm the presence of chromosome territories and the spatial proximity of small, gene-rich chromosomes. We identified an additional level of genome organization that is characterized by the spatial segregation of open and closed chromatin to form two genome-wide compartments. At the megabase scale, the chromatin conformation is consistent with a fractal globule, a knot-free, polymer conformation that enables maximally dense packing while preserving the ability to easily fold and unfold any genomic locus. The fractal globule is distinct from the more commonly used globular equilibrium model. Our results demonstrate the power of Hi-C to map the dynamic conformations of whole genomes.