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.

在相间期，真核基因组被组织成染色体区域，这些区域在空间上被分隔为隔室域。相互作用域或染色体的纠缠程度尚不清楚。我们使用人类细胞中的多接触 3C (MC-3C) 分析了一系列共同发生的染色质相互作用，以深入了解染色质的拓扑纠缠。多接触交互表示通过三维 (3D) 染色质空间的渗透路径 (C-walk)。我们发现，在染色体或区室域相互作用的界面上发生的 C-walk 中的相互作用顺序不是随机的。聚合物模拟表明，这种 C-walks 与拓扑绝缘的远端域一致，即未连接。模拟表明，即使是低水平的随机链通过，例如通过拓扑异构酶 II，将导致纠缠、域界面混合增加以及 C-walk 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，在间期，染色体和染色体结构域之间的纠缠很少见。