Bridging nano- and mesoscale nuclear organization with single-molecule microscopy

Chromatin in the cell nucleus is composed of nucleosomes wrapped with DNA, forming a “beads on a string” structure. At the microscale, chromatin self-organizes into dense domains with less-dense interchromatin space in between, which is posited to play a role in separating the DNA into “active” and “repressive” zones stochastically. However, evidence for the relation between the chromatin organization and its biological function is largely based on protein localization studies in fixed cells or extrapolated from population measurements using biochemical approaches. Here, we combine high-resolution lattice light sheet microscopy, super-resolution localization microscopy, and single particle tracking to investigate the relationship between chromatin structure, nucleosome dynamics, and biological functions. Interestingly, we observed that nucleosome motion and packing vary within different chromatin compartments, resemble a glassy dynamic material, and are consistent with a fractal globule model of chromatin.