Departament de Fisica Fonamental, Universitat de Barcelona, Barcelona, Spain.
Biophys J. 2012 Nov 21;103(10):2223-32. doi: 10.1016/j.bpj.2012.08.056. Epub 2012 Nov 20.
A variety of important cellular processes require, for functional purposes, the colocalization of multiple DNA loci at specific time points. In most cases, the physical mechanisms responsible for bringing them in close proximity are still elusive. Here we show that the interaction of DNA loci with a concentration of diffusing molecular factors can induce spontaneously their colocalization, through a mechanism based on a thermodynamic phase transition. We consider up to four DNA loci and different valencies for diffusing molecular factors. In particular, our analysis illustrates that a variety of nontrivial stable spatial configurations is allowed in the system, depending on the details of the molecular factor/DNA binding-sites interaction. Finally, we discuss as a case study an application of our model to the pairing of X chromosome at X inactivation, one of the best-known examples of DNA colocalization. We also speculate on the possible links between X colocalization and inactivation.
多种重要的细胞过程需要将多个 DNA 位点在特定时间点进行共定位,以实现其功能。在大多数情况下,负责将它们拉近的物理机制仍然难以捉摸。在这里,我们表明 DNA 位点与扩散分子因子浓度的相互作用可以通过基于热力学相变的机制自发诱导它们的共定位。我们考虑了四个 DNA 位点和不同价数的扩散分子因子。特别是,我们的分析说明了在系统中允许存在多种非平凡的稳定空间构型,具体取决于分子因子/DNA 结合位点相互作用的细节。最后,我们作为案例研究讨论了我们的模型在 X 染色体失活中 X 染色体配对的应用,这是 DNA 共定位的最著名的例子之一。我们还推测了 X 染色体共定位和失活之间的可能联系。