Journal Article

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

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

2016

Overview

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.

• Publisher: BioMed Central,Springer Nature B.V
• Subject: Animal Genetics and Genomics / Animals / Binding sites / Bioinformatics / Biomedical and Life Sciences / Chromatin / Chromosomes / Chromosomes, Mammalian - chemistry / Chromosomes, Mammalian - genetics / Chromosomes, Mammalian - metabolism / Computational Biology - methods / Deoxyribonucleic acid / DNA / Evolutionary Biology / Experiments / fluorescence in situ hybridization / Gene expression / Gene loci / genome / Genomes / Human Genetics / Humans / In Situ Hybridization, Fluorescence / Life Sciences / mammals / Method / Mice / Microbial Genetics and Genomics / Models, Biological / Models, Molecular / Nucleic Acid Conformation / Plant Genetics and Genomics / Polymers / Population / prediction / Proteins / Regulatory sequences / Regulatory Sequences, Nucleic Acid / Stem cells / The three dimensional organization of the nucleus