Physical Modeling of Dynamic Coupling between Chromosomal Loci
Physical Modeling of Dynamic Coupling between Chromosomal Loci
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DOI：
10.1016/j.bpj.2015.11.3520
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发表时间：
2016-01-19
影响因子：
3.4
通讯作者：
Spakowitz, Andrew J.
中科院分区：
文献类型：
--
作者：
Lampo, Thomas J.;Kennard, Andrew S.;Spakowitz, Andrew J.
染色体DNA的运动对于许多生物过程是必不可少的，包括分离、转录调节、重组和包装。通过对多个基因座的染色体动力学进行预测性定量建模，将大大增强对这些过程的物理理解。使用聚合物动力学框架，我们开发了一个预测的相关性在一个单一的染色体上的两个位点的速度或以其他方式连接的染色质。这些预测表明，可以通过改变轨迹位置测量之间的滞后时间来识别两个轨迹之间的相关运动的签名。一般来说，该理论预测，随着滞后时间间隔的增加，双轨迹动态行为从完全不相关转变为有效的单轨迹行为。这种转变对应于通过中间段的位点之间的应力通信的时间尺度。这个相对简单的框架，使定量预测的基础上，一个单一的时间尺度拟合参数，可以直接比较荧光标记的染色体基因座的体内运动。此外，该理论框架使得能够从其相关运动的签名检测动态耦合的染色体区域。
The motion of chromosomal DNA is essential to many biological processes, including segregation, transcriptional regulation, recombination, and packaging. Physical understanding of these processes would be dramatically enhanced through predictive, quantitative modeling of chromosome dynamics of multiple loci. Using a polymer dynamics framework, we develop a prediction for the correlation in the velocities of two loci on a single chromosome or otherwise connected by chromatin. These predictions reveal that the signature of correlated motion between two loci can be identified by varying the lag time between locus position measurements. In general, this theory predicts that as the lag time interval increases, the dual-loci dynamic behavior transitions from being completely uncorrelated to behaving as an effective single locus. This transition corresponds to the timescale of the stress communication between loci through the intervening segment. This relatively simple framework makes quantitative predictions based on a single timescale fit parameter that can be directly compared to the in vivo motion of fluorescently labeled chromosome loci. Furthermore, this theoretical framework enables the detection of dynamically coupled chromosome regions from the signature of their correlated motion.