论文标题

转录诱导的活性力抑制染色质运动

Transcription-induced active forces suppress chromatin motion

论文作者

Shin, Sucheol, Shi, Guang, Cho, Hyun Woo, Thirumalai, D.

论文摘要

由于各种实验技术的进步,许多物种中的相间染色体的组织开始出现。但是,关于动力学的知之甚少,尤其是在染色质的功能状态下。一些实验表明,在人体相间染色体中,单个基因座在转录过程中的运动能力降低,并在抑制转录后增加。这是一个违反直觉的发现,因为人们认为,由RNA聚合酶II(RNAPII)生成的十个Pico-Newtons的活性机械力($ f $)可能会传播到染色质的富基因区域,它会使它更开放,从而增强了移动性。我们开发了一种用于相间染色体的最小活性共聚物模型,以研究$ f $如何影响染色质的动力学特性。富含基因区域的基因座的运动在$ f $的中间范围内被抑制,并且在小$ f $值下得到增强,这在实验中也已经观察到。在中间$ f $中,连续基因座之间的键长增加,与非键位基因座之间有吸引力的相互作用的最小距离相称。这会导致瞬态疾病的转变,导致转录过程中的迁移率降低。令人惊讶的是,基因座动力学的$ f $依赖性变化保留了染色体的组织为$ f = 0 $。该基因座的瞬时排序在具有随机表观遗传特征的聚合物中未发现,在富基因的区域中可能是一种合理的机制,可以使涉及转录因子,RNAPII和染色质素的动态网络核定。

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 counter-intuitive finding because it is thought that the active mechanical force ($F$) on the order of ten pico-newtons, 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 non-bonded 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 $F=0$. 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.

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