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利用生物信息数据和聚合物模型预测哺乳动物基因组中顺式调控区域的三维折叠。

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

作者信息

Brackley Chris A, Brown Jill M, Waithe Dominic, Babbs Christian, Davies James, Hughes Jim R, Buckle Veronica J, Marenduzzo Davide

机构信息

SUPA, School of Physics and Astronomy, University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JZ, UK.

MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, OX3 9DS, UK.

出版信息

Genome Biol. 2016 Mar 31;17:59. doi: 10.1186/s13059-016-0909-0.

Abstract

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.

摘要

可以使用诸如Capture-C等方法来探究染色体的三维(3D)组织。然而,目前尚不清楚这种群体水平的数据如何与单个细胞内的组织相关,并且导致观察到的相互作用的机制在很大程度上仍然不清楚。我们提出了一种聚合物建模方案,其基于染色体结构由形成染色质环的蛋白质桥维持这一假设。为了测试该模型,我们进行了荧光原位杂交(FISH)实验并与Capture-C数据进行比较。仅从蛋白质结合位点的位置出发,我们的模型就能准确预测实验观察到的染色质相互作用,揭示出一系列三维构象。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/49ac/4815170/0e1f941a64bc/13059_2016_909_Fig3_HTML.jpg

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