Condensed Chromatin Behaves like a Solid on the Mesoscale In Vitro and in Living Cells

The association of nuclear DNA with histones to form chromatin is essential for temporal and spatial control of eukaryotic genomes. In this study, we examined the physical state of condensed chromatin in vitro and in vivo. Our in vitro studies demonstrate that self-association of nucleosomal arrays under a wide range of solution conditions produces supramolecular condensates in which the chromatin is physically constrained and solid-like. By measuring DNA mobility in living cells, we show that condensed chromatin also exhibits solid-like behavior in vivo. Representative heterochromatin proteins, however, display liquid-like behavior and coalesce around the solid chromatin scaffold. Importantly, euchromatin and heterochromatin show solid-like behavior even under conditions that produce limited interactions between chromatin fibers. Our results reveal that condensed chromatin exists in a solid-like state whose properties resist external forces and create an elastic gel and provides a scaffold that supports liquid-liquid phase separation of chromatin binding proteins. [Display omitted] •Nucleosome arrays and isolated chromatin are solids under physiological conditions•Chromatin is solid-like in living cells in high- and low-chromatin-density regions•Histone acetylation disperses but does not liquify chromatin•Solid chromatin scaffold supports liquid phase-separated compartments Chromatin in live cells functions as a solid material and provides a scaffold for spatial organization of nuclear components that can adopt a liquid-like state.