Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, USA.
Howard Hughes Medical Institute, Chevy Chase, MD, USA.
Nat Struct Mol Biol. 2020 Dec;27(12):1105-1114. doi: 10.1038/s41594-020-0506-5. Epub 2020 Sep 14.
During interphase, the eukaryotic genome is organized into chromosome territories that are spatially segregated into compartment domains. The extent to which interacting domains or chromosomes are entangled is not known. We analyze series of co-occurring chromatin interactions using multi-contact 3C (MC-3C) in human cells to provide insights into the topological entanglement of chromatin. Multi-contact interactions represent percolation paths (C-walks) through three-dimensional (3D) chromatin space. We find that the order of interactions within C-walks that occur across interfaces where chromosomes or compartment domains interact is not random. Polymer simulations show that such C-walks are consistent with distal domains being topologically insulated, that is, not catenated. Simulations show that even low levels of random strand passage, for example by topoisomerase II, would result in entanglements, increased mixing at domain interfaces and an order of interactions within C-walks not consistent with experimental MC-3C data. Our results indicate that, during interphase, entanglements between chromosomes and chromosomal domains are rare.
在有丝分裂间期，真核基因组组织成染色体域，这些域在空间上分隔成隔室域。相互作用的域或染色体纠缠的程度尚不清楚。我们使用人类细胞中的多接触 3C（MC-3C）分析一系列同时发生的染色质相互作用，以深入了解染色质的拓扑缠结。多接触相互作用代表通过三维（3D）染色质空间的渗流路径（C-行走）。我们发现，发生在染色体或隔室域相互作用界面处的 C-行走内的相互作用顺序不是随机的。聚合物模拟表明，这种 C-行走与远端域的拓扑隔离一致，即不连环。模拟表明，即使是低水平的随机链通过，例如拓扑异构酶 II，也会导致缠结、域界面处的混合增加以及 C-行走内的相互作用顺序与实验 MC-3C 数据不一致。我们的结果表明，在有丝分裂间期，染色体和染色体域之间的缠结很少见。
