Institute for Theoretical Physics, University of Heidelberg, Philosophenweg 19, D-69120 Heidelberg, Germany.
Nucleic Acids Res. 2012 Feb;40(3):972-80. doi: 10.1093/nar/gkr779. Epub 2011 Oct 5.
What physical mechanism leads to organization of a highly condensed and confined circular chromosome? Computational modeling shows that confinement-induced organization is able to overcome the chromosome's propensity to mix by the formation of topological domains. The experimentally observed high precision of separate subcellular positioning of loci (located on different chromosomal domains) in Escherichia coli naturally emerges as a result of entropic demixing of such chromosomal loops. We propose one possible mechanism for organizing these domains: regulatory control defined by the underlying E. coli gene regulatory network requires the colocalization of transcription factor genes and target genes. Investigating this assumption, we find the DNA chain to self-organize into several topologically distinguishable domains where the interplay between the entropic repulsion of chromosomal loops and their compression due to the confining geometry induces an effective nucleoid filament-type of structure. Thus, we propose that the physical structure of the chromosome is a direct result of regulatory interactions. To reproduce the observed precise ordering of the chromosome, we estimate that the domain sizes are distributed between 10 and 700 kb, in agreement with the size of topological domains identified in the context of DNA supercoiling.
是什么物理机制导致高度浓缩和受限的环状染色体的组织？计算模型表明，限制诱导的组织能够通过拓扑域的形成克服染色体混合的趋势。在大肠杆菌中，实验观察到的不同染色体区域（位于不同染色体区域的基因）在亚细胞位置上的高度精确分离，这是由于这种染色体环的熵分离而自然出现的。我们提出了一种组织这些区域的可能机制：由大肠杆菌基因调控网络定义的调控控制需要转录因子基因和靶基因的共定位。研究这一假设，我们发现 DNA 链可以自我组织成几个拓扑上可区分的域，其中染色体环的熵排斥及其因约束几何形状而产生的压缩之间的相互作用诱导出一种有效的核小体丝状结构。因此，我们提出染色体的物理结构是调控相互作用的直接结果。为了再现观察到的染色体的精确排序，我们估计域的大小分布在 10kb 到 700kb 之间，这与在 DNA 超螺旋化背景下确定的拓扑域的大小一致。
