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

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.

Authors: Nozaki T, Shinkai S, Ide S, Higashi K, Tamura S, Shimazoe MA, Nakagawa M, Suzuki Y, Okada Y, Sasai M, Onami S, Kurokawa K, Iida S, Maeshima K

Journal: SCIENCE ADVANCES. 2023; 5;9(14):eadf1488.

DOI: https://www.science.org/doi/10.1126/sciadv.adf1488