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RIKEN Advanced Science Institute, Hokkaido University, 현 서울아산병원

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Cell Reports, 2012 Dec 27;2(6):1645-56 | https://doi.org/10.1016/j.celrep.2012.11.008 Local Nucleosome Dynamics Facilitate Chromatin Accessibility in Living Mammalian Cells

Saera Hihara ^{1 2 11}, Chan-Gi Pack ^{3 6 11}, Kazunari Kaizu ^{8 11}, Tomomi Tani ^{7 12}, Tomo Hanafusa ¹, Tadasu Nozaki ^{1 9}, Satoko Takemoto ⁴, Tomohiko Yoshimi ¹⁰, Hideo Yokota ⁴, Naoko Imamoto ⁵, Yasushi Sako ³, Masataka Kinjo ⁶, Koichi Takahashi ^{8 9}, Takeharu Nagai ^{7 13}, Kazuhiro Maeshima ^{1 2 5 *}

¹Biological Macromolecules Laboratory, Structural Biology Center, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan
²Department of Genetics, School of Life Science, Graduate University for Advanced Studies (Sokendai), Mishima, Shizuoka 411-8540, Japan
³Cellular Informatics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351- 0198, Japan
⁴Bio-research Infrastructure Construction Team, RIKEN Advanced Science Institute, Wako, Saitama 351- 0198, Japan
⁵Cellular Dynamics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351- 0198, Japan
⁶Laboratory of Molecular Cell Dynamics, Hokkaido University, Sapporo 001-0021, Japan
⁷Research Institute for Electronic Science, Hokkaido University, Sapporo 001-0021, Japan
⁸Laboratory for Biochemical Simulation, RIKEN Quantitative Biology Center, Suita, Osaka 565-0874, Japan
⁹Institute for Advanced Biosciences, Keio University, Fujisawa 252-8520, Japan
¹⁰Department of Bioengineering, Graduate School of Engineering Osaka City University, Osaka 558-8585, Japan
¹¹These authors contributed equally to this work
¹²Present address: Cellular Dynamics Program, Marine Biological Laboratory, Woods Hole, MA 02543, USA
¹³Present address: The Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan

^*Corresponding author: correspondence to Kazuhiro Maeshima

Abstract

Genome information, which is three-dimensionally organized within cells as chromatin, is searched and read by various proteins for diverse cell functions. Although how the protein factors find their targets remains unclear, the dynamic and flexible nature of chromatin is likely crucial. Using a combined approach of fluorescence correlation spectroscopy, single-nucleosome imaging, and Monte Carlo computer simulations, we demonstrate local chromatin dynamics in living mammalian cells. We show that similar to interphase chromatin, dense mitotic chromosomes also have considerable chromatin accessibility. For both interphase and mitotic chromatin, we observed local fluctuation of individual nucleosomes (∼50 nm movement/30 ms), which is caused by confined Brownian motion. Inhibition of these local dynamics by crosslinking impaired accessibility in the dense chromatin regions. Our findings show that local nucleosome dynamics drive chromatin accessibility. We propose that this local nucleosome fluctuation is the basis for scanning genome information.

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