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

被引:80
作者
Brackley, Chris A. [1 ]
Brown, Jill M. [2 ]
Waithe, Dominic [3 ]
Babbs, Christian [2 ]
Davies, James [2 ]
Hughes, Jim R. [2 ]
Buckle, Veronica J. [2 ]
Marenduzzo, Davide [1 ]
机构
[1] Univ Edinburgh, Sch Phys & Astron, SUPA, Mayfield Rd, Edinburgh EH9 3JZ, Midlothian, Scotland
[2] Univ Oxford, Weatherall Inst Mol Med, Mol Haematol Unit, MRC, Oxford OX3 9DS, England
[3] Univ Oxford, Weatherall Inst Mol Med, Wolfson Imaging Ctr Oxford, Oxford OX3 9DS, England
基金
欧洲研究理事会; 英国工程与自然科学研究理事会; 英国医学研究理事会;
关键词
Chromosome conformation; Polymer model; Fluorescence in situ hybridization; cis-regulation; BETA-GLOBIN LOCUS; NUCLEAR LAMINA INTERACTIONS; PRIMARY ERYTHROID-CELLS; CHROMOSOME CONFORMATION; DOMAIN ORGANIZATION; GENE-EXPRESSION; CHROMATIN; CTCF; TRANSCRIPTION; SINGLE;
D O I
10.1186/s13059-016-0909-0
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 090105 [作物生产系统与生态工程];
摘要
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.
引用
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页数:16
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