title: Dynamic Nucleosome Movement Provides Structural Information of Topological Chromatin Domains in Living Human Cells.
abstract: The mammalian genome is organized into submegabase-sized chromatin domains (CDs) including topologically associating domains, which have been identified using chromosome conformation capture-based methods. Single-nucleosome imaging in living mammalian cells has revealed subdiffusively dynamic nucleosome movement. It is unclear how single nucleosomes within CDs fluctuate and how the CD structure reflects the nucleosome movement. Here, we present a polymer model wherein CDs are characterized by fractal dimensions and the nucleosome fibers fluctuate in a viscoelastic medium with memory. We analytically show that the mean-squared displacement (MSD) of nucleosome fluctuations within CDs is subdiffusive. The diffusion coefficient and the subdiffusive exponent depend on the structural information of CDs. This analytical result enabled us to extract information from the single-nucleosome imaging data for HeLa cells. Our observation that the MSD is lower at the nuclear periphery region than the interior region indicates that CDs in the heterochromatin-rich nuclear periphery region are more compact than those in the euchromatin-rich interior region with respect to the fractal dimensions as well as the size. Finally, we evaluated that the average size of CDs is in the range of 100-500 nm and that the relaxation time of nucleosome movement within CDs is a few seconds. Our results provide physical and dynamic insights into the genome architecture in living cells.
authors.affiliation: Research Center for the Mathematics on Chromatin Live Dynamics (RcMcD), Hiroshima University, Higashi-Hiroshima, Japan.
authors.forename: Soya
authors.initials: S
authors.lastname: Shinkai
authors.affiliation: Biological Macromolecules Laboratory, Structural Biology Center, National Institute of Genetics, Mishima, Japan.|Institute for Advanced Biosciences, Keio University, Fujisawa, Japan.
authors.forename: Tadasu
authors.initials: T
authors.lastname: Nozaki
authors.affiliation: Biological Macromolecules Laboratory, Structural Biology Center, National Institute of Genetics, Mishima, Japan.|Department of Genetics, School of Life Science, Graduate University for Advanced Studies (Sokendai), Mishima, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Maeshima
authors.affiliation: Research Center for the Mathematics on Chromatin Live Dynamics (RcMcD), Hiroshima University, Higashi-Hiroshima, Japan.
authors.forename: Yuichi
authors.identifier: http://orcid.org/0000-0003-0032-2424
authors.initials: Y
authors.lastname: Togashi
mesh_terms: D001665:Binding Sites; D002843:Chromatin / Q000737:chemistry* / Q000235:genetics* / Q000648:ultrastructure; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D003198:Computer Simulation; D006367:HeLa Cells; D006801:Humans; D008956:Models, Chemical; D008957:Models, Genetic; D008958:Models, Molecular; D008968:Molecular Conformation; D057054:Molecular Imaging / Q000379:methods*; D009038:Motion; D009707:Nucleosomes / Q000737:chemistry* / Q000235:genetics* / Q000648:ultrastructure
chemical_list: D002843:Chromatin; D009707:Nucleosomes