Benedetti Fabrizio, Racko Dusan, Dorier Julien, Burnier Yannis, Stasiak Andrzej
Center for Integrative Genomics, University of Lausanne, 1015 Lausanne, Switzerland.
Vital-IT, SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
Nucleic Acids Res. 2017 Sep 29;45(17):9850-9859. doi: 10.1093/nar/gkx716.
The question of how self-interacting chromatin domains in interphase chromosomes are structured and generated dominates current discussions on eukaryotic chromosomes. Numerical simulations using standard polymer models have been helpful in testing the validity of various models of chromosome organization. Experimental contact maps can be compared with simulated contact maps and thus verify how good is the model. With increasing resolution of experimental contact maps, it became apparent though that active processes need to be introduced into models to recapitulate the experimental data. Since transcribing RNA polymerases are very strong molecular motors that induce axial rotation of transcribed DNA, we present here models that include such rotational motors. We also include into our models swivels and sites for intersegmental passages that account for action of DNA topoisomerases releasing torsional stress. Using these elements in our models, we show that transcription-induced supercoiling generated in the regions with divergent-transcription and supercoiling relaxation occurring between these regions are sufficient to explain formation of self-interacting chromatin domains in chromosomes of fission yeast (S. pombe).
间期染色体中自相互作用染色质结构域如何构建和形成的问题主导着当前关于真核染色体的讨论。使用标准聚合物模型进行的数值模拟有助于检验各种染色体组织模型的有效性。实验性接触图谱可与模拟接触图谱进行比较，从而验证模型的优劣。然而，随着实验性接触图谱分辨率的提高，很明显需要将活跃过程引入模型以重现实验数据。由于正在转录的RNA聚合酶是非常强大的分子马达，可诱导转录DNA的轴向旋转，我们在此展示包含此类旋转马达的模型。我们还在模型中纳入了旋转接头和节段间通道位点，以解释释放扭转应力的DNA拓扑异构酶的作用。在我们的模型中使用这些元素，我们表明在转录方向相反的区域产生的转录诱导超螺旋以及这些区域之间发生的超螺旋松弛足以解释裂殖酵母（粟酒裂殖酵母）染色体中自相互作用染色质结构域的形成。
