Transferable model for chromosome architecture
Transferable model for chromosome architecture
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DOI：
10.1073/pnas.1613607113
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发表时间：
2016-10-25
影响因子：
11.1
通讯作者：
Onuchic, Jose N.
中科院分区：
文献类型：
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作者：
Di Pierro, Michele;Zhang, Bin;Onuchic, Jose N.
在活体中，人类基因组折叠成一个独特的3D结构集合。推动折叠过程的机制仍不清楚。我们报道了一个染色质(最小染色质模型)的理论模型，该模型解释了间期染色体的折叠，并产生了与实验数据一致的染色体构象。该模型的能量图是利用最大熵原理得出的，并依赖于两个实验得出的输入：染色质类型的轨迹分类和染色质环位置的目录。首先，我们使用人类GM12878淋巴母细胞10号染色体的Hi-C接触图来训练我们的能量函数。然后，我们使用该模型进行了分子动力学模拟，生成了所有GM12878常染色体的3D结构集合。最后，我们使用这些3D结构来生成联系人地图。我们发现，对于所有GM12878常染色体，模拟的接触图与实验结果非常吻合。这些模拟得到的结构集合显示出染色体未打结，染色质类型的相分离，以及开放染色质位于染色体区域边缘的趋势。
In vivo, the human genome folds into a characteristic ensemble of 3D structures. The mechanism driving the folding process remains unknown. We report a theoretical model for chromatin (Minimal Chromatin Model) that explains the folding of interphase chromosomes and generates chromosome conformations consistent with experimental data. The energy landscape of the model was derived by using the maximum entropy principle and relies on two experimentally derived inputs: a classification of loci into chromatin types and a catalog of the positions of chromatin loops. First, we trained our energy function using the Hi-C contact map of chromosome 10 from human GM12878 lymphoblastoid cells. Then, we used the model to perform molecular dynamics simulations producing an ensemble of 3D structures for all GM12878 autosomes. Finally, we used these 3D structures to generate contact maps. We found that simulated contact maps closely agree with experimental results for all GM12878 autosomes. The ensemble of structures resulting from these simulations exhibited unknotted chromosomes, phase separation of chromatin types, and a tendency for open chromatin to lie at the periphery of chromosome territories.