Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School (UMMS), 368 Plantation Street, Worcester, MA 01605-0103, USA.
Science. 2013 Nov 22;342(6161):948-53. doi: 10.1126/science.1236083. Epub 2013 Nov 7.
Mitotic chromosomes are among the most recognizable structures in the cell, yet for over a century their internal organization remains largely unsolved. We applied chromosome conformation capture methods, 5C and Hi-C, across the cell cycle and revealed two distinct three-dimensional folding states of the human genome. We show that the highly compartmentalized and cell type-specific organization described previously for nonsynchronous cells is restricted to interphase. In metaphase, we identified a homogenous folding state that is locus-independent, common to all chromosomes, and consistent among cell types, suggesting a general principle of metaphase chromosome organization. Using polymer simulations, we found that metaphase Hi-C data are inconsistent with classic hierarchical models and are instead best described by a linearly organized longitudinally compressed array of consecutive chromatin loops.
有丝分裂染色体是细胞中最容易识别的结构之一，但一个多世纪以来，它们的内部结构在很大程度上仍未得到解决。我们应用染色体构象捕获方法 5C 和 Hi-C 进行了整个细胞周期的研究，揭示了人类基因组的两种截然不同的三维折叠状态。我们表明，以前描述的非同步细胞中高度分隔和细胞类型特异性的组织仅限于间期。在中期，我们确定了一种均质折叠状态，该状态与位置无关，存在于所有染色体中，并且在细胞类型之间一致，这表明了中期染色体组织的一般原则。使用聚合物模拟，我们发现中期 Hi-C 数据与经典层次模型不一致，而是最好用线性组织的连续染色质环的纵向压缩阵列来描述。
