Condensed but liquid-like domain organization of active chromatin regions in living human cells

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  • Tadasu Nozaki
    Genome Dynamics Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
  • Soya Shinkai
    Laboratory for Developmental Dynamics, Center for Biosystems Dynamics Research (BDR), RIKEN, Kobe, Hyogo 650-0047, Japan.
  • Satoru Ide
    Genome Dynamics Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
  • Koichi Higashi
    Department of Genetics, School of Life Science, SOKENDAI (Graduate University for Advanced Studies), Mishima, Shizuoka 411-8540, Japan.
  • Sachiko Tamura
    Genome Dynamics Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
  • Masa A. Shimazoe
    Genome Dynamics Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
  • Masaki Nakagawa
    Department of Computer Science and Engineering, Fukuoka Institute of Technology, Fukuoka, Fukuoka 811-0295, Japan.
  • Yutaka Suzuki
    Department of Computational Biology and Medical Sciences, University of Tokyo, 5-1-5 Kashiwanoha Kashiwa, Chiba 277-8562, Japan.
  • Yasushi Okada
    Laboratory for Cell Polarity Regulation, Center for Biosystems Dynamics Research (BDR), RIKEN, Suita, Osaka 565-0874, Japan.
  • Masaki Sasai
    Department of Complex Systems Science, Nagoya University, Nagoya 464-8601, Japan.
  • Shuichi Onami
    Laboratory for Developmental Dynamics, Center for Biosystems Dynamics Research (BDR), RIKEN, Kobe, Hyogo 650-0047, Japan.
  • Ken Kurokawa
    Department of Genetics, School of Life Science, SOKENDAI (Graduate University for Advanced Studies), Mishima, Shizuoka 411-8540, Japan.
  • Shiori Iida
    Genome Dynamics Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
  • Kazuhiro Maeshima
    Genome Dynamics Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.

抄録

<jats:p>In eukaryotes, higher-order chromatin organization is spatiotemporally regulated as domains, for various cellular functions. However, their physical nature in living cells remains unclear (e.g., condensed domains or extended fiber loops; liquid-like or solid-like). Using novel approaches combining genomics, single-nucleosome imaging, and computational modeling, we investigated the physical organization and behavior of early DNA replicated regions in human cells, which correspond to Hi-C contact domains with active chromatin marks. Motion correlation analysis of two neighbor nucleosomes shows that nucleosomes form physically condensed domains with ~150-nm diameters, even in active chromatin regions. The mean-square displacement analysis between two neighbor nucleosomes demonstrates that nucleosomes behave like a liquid in the condensed domain on the ~150 nm/~0.5 s spatiotemporal scale, which facilitates chromatin accessibility. Beyond the micrometers/minutes scale, chromatin seems solid-like, which may contribute to maintaining genome integrity. Our study reveals the viscoelastic principle of the chromatin polymer; chromatin is locally dynamic and reactive but globally stable.</jats:p>

収録刊行物

  • Science Advances

    Science Advances 9 (14), 2023-04-07

    American Association for the Advancement of Science (AAAS)

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