Local Nucleosome Dynamics Facilitate Chromatin Accessibility in Living Mammalian Cells

• Published in: Cell reports (Cambridge) 2012-12, Vol.2 (6), p.1645-1656
• Main Authors: Hihara, Saera, Pack, Chan-Gi, Kaizu, Kazunari, Tani, Tomomi, Hanafusa, Tomo, Nozaki, Tadasu, Takemoto, Satoko, Yoshimi, Tomohiko, Yokota, Hideo, Imamoto, Naoko, Sako, Yasushi, Kinjo, Masataka, Takahashi, Koichi, Nagai, Takeharu, Maeshima, Kazuhiro
• Format: Article
• Language: English
• Subjects: Cell Line; Chromatin Assembly and Disassembly - physiology; Chromosomes, Human - metabolism; Computer Simulation; Humans; Interphase - physiology; Microscopy, Fluorescence; Models, Biological; Nucleosomes - metabolism
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2012.11.008

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. [Display omitted] ► Dense chromatin regions have considerable chromatin accessibility ► Observed local fluctuation of individual nucleosomes in interphase and mitotic chromatin ► Inhibition of nucleoome fluctuation impaired the chromatin accessibility ► Local fluctuation of nucleosomes is the basis for scanning genome information Various proteins scan long genomic DNA, which is organized as chromatin within the cell nucleus, to read out genetic information. However, how protein factors find their target information remains unclear. Using a combined in vivo/in silico strategy, Maeshima and colleagues show that a chromatin fluctuation, driven by Brownian motion, plays an important role in this process. Chromatin fluctuation facilitates chromatin accessibility and is the basis for scanning genome information.