Dynamic Nucleosome Movement Provides Structural Information of Topological Chromatin Domains in Living Human Cells

PLoS Comput Biol. 2016 Oct 20;12(10):e1005136. doi: 10.1371/journal.pcbi.1005136. eCollection 2016 Oct.

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.

MeSH terms

  • Binding Sites
  • Chromatin / chemistry*
  • Chromatin / genetics*
  • Chromatin / ultrastructure
  • Chromatin Assembly and Disassembly / genetics
  • Computer Simulation
  • HeLa Cells
  • Humans
  • Models, Chemical*
  • Models, Genetic
  • Models, Molecular
  • Molecular Conformation
  • Molecular Imaging / methods*
  • Motion
  • Nucleosomes / chemistry*
  • Nucleosomes / genetics*
  • Nucleosomes / ultrastructure

Substances

  • Chromatin
  • Nucleosomes

Grants and funding

This research is supported by: Platform Project for Supporting in Drug Discovery and Life Science Research (Platform for Dynamic Approaches to Living System) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT; http://www.mext.go.jp/english/) and the Japan Agency for Medical Research and Development (AMED; http://www.amed.go.jp/en/); MEXT KAKENHI (JP16H01408 to SS, JP23115007 to YT, and JP23115005 to KM), and Research Fellowship for Young Scientists (JP13J04821 and JP16J07205) to TN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.