Nonequilibrium Biophysical Processes Influence the Large-Scale Architecture of the Cell Nucleus
Nonequilibrium Biophysical Processes Influence the Large-Scale Architecture of the Cell Nucleus
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DOI：
10.1016/j.bpj.2019.11.017
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发表时间：
2020-05-05
影响因子：
3.4
通讯作者：
Menon, Gautam, I
中科院分区：
文献类型：
--
作者：
Agrawal, Ankit;Ganai, Nirmalendu;Menon, Gautam, I
传统上，核结构的模型方法忽略了作用于染色质的ATP燃料的活性过程的生物物理后果。然而，转录偶联活动是一种随机力的来源，这种随机力比生理温度下存在的布朗力大得多。在这里，我们描述了一种在后生动物中结合特定细胞类型的活动过程的大规模核结构的方法。该模型预测了每个染色体的位置分布、形状和重叠的统计数据。对该模型的模拟再现了在间期跨越人类细胞核的大规模核结构背后的共同组织原则。这些问题包括常染色质和异染色质的差异定位、染色体的区域组织(包括基于基因密度和基于大小的染色体径向定位方案)、染色体区域的非随机位置以及单个染色体的形状统计。我们认为，转录活性在染色体上分布的生物物理结果应该是任何染色体定位密码的中心。
Model approaches to nuclear architecture have traditionally ignored the biophysical consequences of ATP-fueled active processes acting on chromatin. However, transcription-coupled activity is a source of stochastic forces that are substantially larger than the Brownian forces present at physiological temperatures. Here, we describe an approach to large-scale nuclear architecture in metazoans that incorporates cell-type-specific active processes. The model predicts the statistics of positional distributions, shapes, and overlaps of each chromosome. Simulations of the model reproduce common organizing principles underlying large-scale nuclear architecture across human cell nuclei in interphase. These include the differential positioning of euchromatin and heterochromatin, the territorial organization of chromosomes (including both gene-density-based and size-based chromosome radial positioning schemes), the nonrandom locations of chromosome territories, and the shape statistics of individual chromosomes. We propose that the biophysical consequences of the distribution of transcriptional activity across chromosomes should be central to any chromosome positioning code.