Epigenomics Project, Genopole, CNRS UPS 3201, UniverSud Paris, University of Evry, Genopole Campus 1-Genavenir 6, Evry, France.
PLoS Comput Biol. 2010 Feb 12;6(2):e1000678. doi: 10.1371/journal.pcbi.1000678.
Transcriptional activity has been shown to relate to the organization of chromosomes in the eukaryotic nucleus and in the bacterial nucleoid. In particular, highly transcribed genes, RNA polymerases and transcription factors gather into discrete spatial foci called transcription factories. However, the mechanisms underlying the formation of these foci and the resulting topological order of the chromosome remain to be elucidated. Here we consider a thermodynamic framework based on a worm-like chain model of chromosomes where sparse designated sites along the DNA are able to interact whenever they are spatially close by. This is motivated by recurrent evidence that there exist physical interactions between genes that operate together. Three important results come out of this simple framework. First, the resulting formation of transcription foci can be viewed as a micro-phase separation of the interacting sites from the rest of the DNA. In this respect, a thermodynamic analysis suggests transcription factors to be appropriate candidates for mediating the physical interactions between genes. Next, numerical simulations of the polymer reveal a rich variety of phases that are associated with different topological orderings, each providing a way to increase the local concentrations of the interacting sites. Finally, the numerical results show that both one-dimensional clustering and periodic location of the binding sites along the DNA, which have been observed in several organisms, make the spatial co-localization of multiple families of genes particularly efficient.
转录活性已被证明与真核细胞核和细菌拟核中染色体的组织有关。特别是，高度转录的基因、RNA 聚合酶和转录因子聚集到称为转录工厂的离散空间焦点中。然而，这些焦点形成的机制以及染色体的拓扑顺序仍然需要阐明。在这里，我们考虑了一个基于染色体的蠕虫样链模型的热力学框架，其中 DNA 上的稀疏指定位置只要在空间上接近，就能够相互作用。这是因为有反复的证据表明，一起运作的基因之间存在物理相互作用。这个简单的框架产生了三个重要的结果。首先，转录焦点的形成可以看作是相互作用的位点与 DNA 其余部分的微相分离。在这方面，热力学分析表明转录因子是介导基因之间物理相互作用的合适候选者。其次，聚合物的数值模拟揭示了与不同拓扑排序相关的多种相，每种相都提供了一种增加相互作用位点局部浓度的方法。最后，数值结果表明，在几种生物中观察到的 DNA 上结合位点的一维聚类和周期性定位，使得多个基因家族的空间共定位特别有效。
