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Abstract：
The organization of interphase chromosomes in a number of species is starting to emerge thanks to advances in a variety of experimental techniques. However, much less is known about the dynamics, especially in the functional states of chromatin. Some experiments have shown that the motility of individual loci in human interphase chromosome decreases during transcription and increases upon inhibiting transcription. This is a counterintuitive finding because it is thought that the active mechanical force (F) on the order of ten piconewtons, generated by RNA polymerase II (RNAPII) that is presumably transmitted to the gene-rich region of the chromatin, would render it more open, thus enhancing the mobility. We developed a minimal active copolymer model for interphase chromosomes to investigate how F affects the dynamical properties of chromatin. The movements of the loci in the gene-rich region are suppressed in an intermediate range of F and are enhanced at small F values, which has also been observed in experiments. In the intermediate F, the bond length between consecutive loci increases, becoming commensurate with the distance at the minimum of the attractive interaction between nonbonded loci. This results in a transient disorder-to-order transition, leading to a decreased mobility during transcription. Strikingly, the F-dependent change in the locus dynamics preserves the organization of the chromosome at [Formula: see text]. Transient ordering of the loci, which is not found in the polymers with random epigenetic profiles, in the gene-rich region might be a plausible mechanism for nucleating a dynamic network involving transcription factors, RNAPII, and chromatin.
摘要：
由于各种实验技术的进步，许多物种中的间期染色体的组织开始出现。然而,对动力学知之甚少，特别是在染色质的功能状态。一些实验表明，人类间期染色体中单个基因座的运动性在转录过程中降低，而在抑制转录时增加。这是一个违反直觉的发现，因为人们认为大约十个皮牛顿的主动机械力（F），由RNA聚合酶II（RNAPII）产生，可能会传递到染色质的基因丰富区域，会让它变得更加开放，从而提高流动性。我们为相间染色体开发了最小活性共聚物模型，以研究F如何影响染色质的动力学特性。基因丰富区域中的基因座的运动在F的中间范围内受到抑制，并在较小的F值下得到增强，在实验中也观察到了这一点。在中间F中，连续基因座之间的键长增加，与非结合基因座之间的有吸引力的相互作用最小时的距离相称。这导致了短暂的无序到有序的转变，导致转录过程中的移动性降低。引人注目的是，基因座动力学中的F依赖性变化保留了染色体在[公式：见正文]处的组织。基因座的瞬时排序，在具有随机表观遗传特征的聚合物中没有发现，在基因丰富的区域可能是一种合理的机制，用于成核涉及转录因子的动态网络，RNAPII,和染色质。
