Análise matemática revela a arquitetura do genoma humano: mero acaso, fortuita necessidade ou design inteligente?

segunda-feira, outubro 24, 2016

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

Soya Shinkai , Tadasu Nozaki, Kazuhiro Maeshima, Yuichi Togashi


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.

Author Summary

The mammalian genome is partitioned into topological chromatin domains (CDs) in the living cell nuclei. Gene expression is highly regulated within CDs according to their structure, whereas chromatin itself is highly dynamic. This raises the following question: how is the CD structure in such dynamic chromatin? We developed a conceptual framework that unifies chromatin dynamics and structure. Using a polymer model with a fractal domain structure in a viscoelastic medium, we analytically show that nucleosome movement is subdiffusive and depends on CD structure. Hence, structural information can be extracted based on nucleosome movement in living cells with single-particle tracking experiments. This framework provides physical insights into the relationship between dynamic genome organization and gene expression.

Citation: Shinkai S, Nozaki T, Maeshima K, Togashi Y (2016) Dynamic Nucleosome Movement Provides Structural Information of Topological Chromatin Domains in Living Human Cells. PLoS Comput Biol 12(10): e1005136. doi:10.1371/journal.pcbi.1005136

Editor: Alexandre V. Morozov, Rutgers University, UNITED STATES

Received: July 12, 2016; Accepted: September 10, 2016; Published: October 20, 2016

Copyright: © 2016 Shinkai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

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; and the Japan Agency for Medical Research and Development (AMED;; 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.

Competing interests: The authors have declared that no competing interests exist.