Inferring the physical properties of yeast chromatin through Bayesian analysis of whole nucleus simulations.
Inferring the physical properties of yeast chromatin through Bayesian analysis of whole nucleus simulations.
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DOI：
10.1186/s13059-017-1199-x
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发表时间：
2017-05-03
期刊：
影响因子：
12.3
通讯作者：
Zimmer C
中科院分区：
文献类型：
--
作者：
Arbona JM;Herbert S;Fabre E;Zimmer C
染色质的结构和机械性质影响DNA的功能和核结构，但仍然知之甚少。在萌芽酵母中，一个简单的聚合物模型，具有最小的序列特定约束和少量的结构参数，可以解释关于核结构的各种实验数据。然而，假设的染色质属性如何影响模型预测之前并没有系统的研究。我们使用了数百个动态染色体模拟和贝叶斯推断来确定染色质属性，这与一个广泛的数据集一致，该数据集包括来自固定和活细胞成像的数百个测量结果和两个Hi-C研究。我们对染色质纤维的平均特性施加了新的限制，将染色质紧凑度缩小到~53-65个基点/nm，持续长度缩小到~52-85个基点/nm。这些限制反对将20-30纳米的纤维作为基因组中唯一的染色质结构。我们最好的模型与核结构的实验测量提供了更好的匹配，并概括了在长时间尺度上在多个位置上测量的染色质动力学。这项工作极大地提高了我们对酵母染色质机制和染色体结构的理解，并为推断其他生物的染色体特性提供了一个新的分析框架。本文的在线版本(doi：10.1186/s13059-017-1199-x)包含补充材料，授权用户可以使用。
The structure and mechanical properties of chromatin impact DNA functions and nuclear architecture but remain poorly understood. In budding yeast, a simple polymer model with minimal sequence-specific constraints and a small number of structural parameters can explain diverse experimental data on nuclear architecture. However, how assumed chromatin properties affect model predictions was not previously systematically investigated. We used hundreds of dynamic chromosome simulations and Bayesian inference to determine chromatin properties consistent with an extensive dataset that includes hundreds of measurements from imaging in fixed and live cells and two Hi-C studies. We place new constraints on average chromatin fiber properties, narrowing down the chromatin compaction to ~53–65 bp/nm and persistence length to ~52–85 nm. These constraints argue against a 20–30 nm fiber as the exclusive chromatin structure in the genome. Our best model provides a much better match to experimental measurements of nuclear architecture and also recapitulates chromatin dynamics measured on multiple loci over long timescales. This work substantially improves our understanding of yeast chromatin mechanics and chromosome architecture and provides a new analytic framework to infer chromosome properties in other organisms. The online version of this article (doi:10.1186/s13059-017-1199-x) contains supplementary material, which is available to authorized users.