转录有一个机械部件,转录机制或RNA聚合酶(RNAP)在DNA或染色质上的易位动态耦合到染色质扭转。这认为染色质机制是真核转录的可能调节剂,然而,这种调节的模式和机制难以捉摸。这里,我们首先采用统计力学方法对拓扑约束染色质的扭转响应进行建模。我们的模型概括了实验观察到的染色质与裸DNA相比较弱的扭转刚度,并提出了核小体到手性不同状态的结构转变,作为对比扭转力学的驱动力。随机模拟中的染色质力学与RNAP易位耦合,我们揭示了控制RNAP速度的DNA超螺旋和核小体动力学的复杂相互作用。核小体在控制转录动力学中起双重作用。基因体内核小体的空间屏障通过阻碍RNAP运动来抵消转录,而手性过渡通过在扭曲DNA时驱动低恢复扭矩来促进RNAP运动。虽然低解离速率的核小体通常是转录抑制的,高度动态的核小体提供较少的空间屏障,并通过缓冲DNA扭曲增强弱转录基因的转录延伸动力学。我们使用该模型来预测与现有实验数据一致的发芽酵母基因组片段中DNA超螺旋的转录依赖性水平。该模型揭示了DNA超螺旋介导的基因之间相互作用的范例,并做出了可测试的预测,这将指导实验设计。
Transcription has a mechanical component, as the translocation of the transcription machinery or RNA polymerase (RNAP) on DNA or chromatin is dynamically coupled to the chromatin torsion. This posits chromatin mechanics as a possible regulator of eukaryotic transcription, however, the modes and mechanisms of this regulation are elusive. Here, we first take a statistical mechanics approach to model the torsional response of topology-constrained chromatin. Our model recapitulates the experimentally observed weaker torsional stiffness of chromatin compared to bare DNA and proposes structural transitions of
nucleosomes into chirally distinct states as the driver of the contrasting torsional mechanics. Coupling chromatin mechanics with RNAP translocation in stochastic simulations, we reveal a complex interplay of DNA supercoiling and nucleosome dynamics in governing RNAP velocity.
Nucleosomes play a dual role in controlling the transcription dynamics. The steric barrier aspect of
nucleosomes in the gene body counteracts transcription via hindering RNAP motion, whereas the chiral transitions facilitate RNAP motion via driving a low restoring torque upon twisting the DNA. While
nucleosomes with low dissociation rates are typically transcriptionally repressive, highly dynamic
nucleosomes offer less of a steric barrier and enhance the transcription elongation dynamics of weakly transcribed genes via buffering DNA twist. We use the model to predict transcription-dependent levels of DNA supercoiling in segments of the budding yeast genome that are in accord with available experimental data. The model unveils a paradigm of DNA supercoiling-mediated interaction between genes and makes testable predictions that will guide experimental design.