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

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• 作者：Chris A. Brackley ; Jill M. Brown ; Dominic Waithe ; Christian Babbs…
• 关键词：Chromosome conformation ; Polymer model ; Fluorescence in situ hybridization ; cis ; regulation
• 刊名：Genome Biology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：17
• 期：1
• 全文大小：3,833 KB
• 刊物主题：Animal Genetics and Genomics; Human Genetics; Plant Genetics & Genomics; Microbial Genetics and Genomics; Fungus Genetics; Bioinformatics;
• 出版者：BioMed Central
• ISSN：1465-6906

文摘

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.