Correlative single molecule lattice light sheet imaging reveals the dynamic relationship between nucleosomes and the local chromatin environment

Timothy A. Daugird, Yu Shi, Katie L. Holland, Hosein Rostamian, Zhe Liu, Luke D. Lavis, Joseph Rodriguez, Brian D. Strahl and Wesley R. Legant ()
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Timothy A. Daugird: University of North Carolina at Chapel Hill
Yu Shi: North Carolina State University
Katie L. Holland: Howard Hughes Medical Institute
Hosein Rostamian: University of North Carolina at Chapel Hill
Zhe Liu: Howard Hughes Medical Institute
Luke D. Lavis: Howard Hughes Medical Institute
Joseph Rodriguez: National Institute of Environmental Health Sciences
Brian D. Strahl: University of North Carolina at Chapel Hill
Wesley R. Legant: University of North Carolina at Chapel Hill

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: Abstract In the nucleus, biological processes are driven by proteins that diffuse through and bind to a meshwork of nucleic acid polymers. To better understand this interplay, we present an imaging platform to simultaneously visualize single protein dynamics together with the local chromatin environment in live cells. Together with super-resolution imaging, new fluorescent probes, and biophysical modeling, we demonstrate that nucleosomes display differential diffusion and packing arrangements as chromatin density increases whereas the viscoelastic properties and accessibility of the interchromatin space remain constant. Perturbing nuclear functions impacts nucleosome diffusive properties in a manner that is dependent both on local chromatin density and on relative location within the nucleus. Our results support a model wherein transcription locally stabilizes nucleosomes while simultaneously allowing for the free exchange of nuclear proteins. Additionally, they reveal that nuclear heterogeneity arises from both active and passive processes and highlight the need to account for different organizational principles when modeling different chromatin environments.

Date: 2024
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DOI: 10.1038/s41467-024-48562-0

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