title: Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models.
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.
authors.affiliation: SUPA, School of Physics and Astronomy, University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JZ, UK.
authors.forename: Chris A
authors.initials: CA
authors.lastname: Brackley
authors.affiliation: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, OX3 9DS, UK.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Brown
authors.affiliation: Wolfson Imaging Centre Oxford, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, OX3 9DS, UK.
authors.forename: Dominic
authors.initials: D
authors.lastname: Waithe
authors.affiliation: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, OX3 9DS, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Babbs
authors.affiliation: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, OX3 9DS, UK.
authors.forename: James
authors.initials: J
authors.lastname: Davies
authors.affiliation: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, OX3 9DS, UK.
authors.forename: Jim R
authors.initials: JR
authors.lastname: Hughes
authors.affiliation: MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, OX3 9DS, UK.
authors.forename: Veronica J
authors.initials: VJ
authors.lastname: Buckle
authors.affiliation: SUPA, School of Physics and Astronomy, University of Edinburgh, Mayfield Road, Edinburgh, EH9 3JZ, UK. dmarendu@ph.ed.ac.uk.
authors.forename: Davide
authors.initials: D
authors.lastname: Marenduzzo
mesh_terms: D000818:Animals; D033481:Chromosomes, Mammalian / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008954:Models, Biological; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011108:Polymers; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: D011108:Polymers
keywords: Chromosome conformation; Fluorescence in situ hybridization; Polymer model; cis-regulation