Integrated MINFLUX tracking reveals two distinct chromatin dynamics classes across cell types

Area of Science:

• Cellular Biology
• Biophysics
• Genomics

Background:

• Chromatin dynamics are crucial for biological processes and nuclear organization.
• Previous studies show inconsistent chromatin subdiffusion measurements.
• Robust measurements require tracking across a wide dynamic range.

Purpose of the Study:

• To investigate chromatin dynamics across an unprecedented timescale.
• To identify distinct chromatin movement patterns and their underlying mechanisms.
• To assess the implications of observed dynamics for nuclear processes.

Main Methods:

• Utilized MINFLUX microscopy for high-resolution tracking.
• Integrated single-molecule and single-locus tracking techniques.
• Analyzed chromatin movement across seven orders of magnitude in time in five cell types.

Main Results:

• Discovered two distinct, cell-type-specific chromatin dynamics classes.
• Observed strong subdiffusion (α ~0.3) in one class, indicating localized searching.
• Identified a shift from strong to weaker subdiffusion in the second class over time.
• Found dynamics are moderately sensitive to perturbations.
• Predicted extremely short search times for nearby loci (<100 nm) and impractically long times for distant loci (>1 µm).

Conclusions:

• Common chromatin polymer models do not fully explain the observed dynamics.
• The two identified dynamics classes have significant implications for enhancer-promoter interactions and DNA repair.
• Understanding chromatin search dynamics is critical for deciphering nuclear organization and function.