Dynamic Interactions at the Chromatin–Nucleolus Interface in Living Cells

Chromatin organization is fundamental to genome function and cellular processes. Within the cell nucleus, chromatin is embedded in a heterogeneous nuclear environment compartmentalized by nuclear condensates such as nucleoli and nuclear speckles, which influence chromatin organization through chromatin–condensate interfacial interactions. Although these interactions have recently been investigated using mesoscopic phase-field models, their microscopic dynamics—specifically, genomic locus–condensate interactions—remain largely uncharacterized in living cells.

Here, we investigate dynamic interactions at the chromatin–nucleolus interface by simultaneously tracking genomic locus dynamics and nucleolar shape fluctuations in living human cells. Distinct nucleolus-associated loci on different chromosomes were labeled with CRISPR-Sirius, a CRISPR-based live-cell chromatin imaging technique, while nucleoli were visualized using fluorescently tagged proteins of the nucleolar granular component. We found that nucleolus-associated loci dynamically “kiss” and slip on the nucleolar surface, indicating transient chromatin–nucleolus interactions. These dynamics also correlate with the surface tension and bending rigidity of the associated nucleolus. Our findings reveal the dynamic nature of chromatin–nucleolus interactions at the microscale and advance our understanding of chromatin–condensate interplay within the living nucleus.