Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models.

Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models.
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DOI:
10.1186/s13059-016-0909-0
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发表时间:
2016-03-31
期刊:
影响因子:
12.3
通讯作者:
Marenduzzo D
Marenduzzo D
中科院分区:
生物学1区
文献类型:
--
作者:
Brackley CA;Brown JM;Waithe D;Babbs C;Davies J;Hughes JR;Buckle VJ;Marenduzzo D

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染色体的三维(3D)组织可以使用Capture-C等方法进行探测。然而,目前还不清楚这些群体水平的数据如何与单个细胞内的组织相关,导致观察到的相互作用的机制在很大程度上仍然不清楚。我们提出了一个聚合物建模方案的基础上的假设,染色体结构是由蛋白质桥,形成染色质环。为了检验模型,我们进行了FISH实验,并与Capture-C数据进行了比较。仅仅从蛋白质结合位点的位置开始,我们的模型准确地预测了实验观察到的染色质相互作用,揭示了一个人口的3D构象。本文的在线版本(doi:10.1186/s13059-016-0909-0)包含补充材料,可供授权用户使用。
The three-dimensional (3D) organization of chromosomes can be probed using methods like Capture-C. However, it is unclear how such population-level data relate to the organization within a single cell, and the mechanisms leading to the observed interactions are still largely obscure. We present a polymer modeling scheme based on the assumption that chromosome architecture is maintained by protein bridges, which form chromatin loops. To test the model, we perform FISH experiments and compare with Capture-C data. Starting merely from the locations of protein binding sites, our model accurately predicts the experimentally observed chromatin interactions, revealing a population of 3D conformations. The online version of this article (doi:10.1186/s13059-016-0909-0) contains supplementary material, which is available to authorized users.