Local Nucleosome Dynamics Facilitate Chromatin Accessibility in Living Mammalian Cells

SummaryGenome 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.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► 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