Static three-dimensional structures determine fast dynamics between distal loci pairs in interphase chromosomes.

Area of Science:

• Genomics
• Molecular Biology
• Biophysics

Background:

• Live-cell imaging reveals unexpectedly rapid distal dynamics between enhancers and promoters, conflicting with standard polymer models.
• This discordance challenges the established structure-function relationship in chromatin organization.
• A gap exists in understanding how static chromatin structure relates to its dynamic behavior.

Purpose of the Study:

• To develop a predictive theory for chromatin dynamics based on static structural data.
• To reconcile the discrepancy between compact static chromatin organization and rapid dynamic interactions.
• To establish a framework for inferring dynamic behavior from static 3D structures.

Main Methods:

• Developed a novel theory to predict chromatin dynamics.
• Accurately determined three-dimensional (3D) chromatin structures from static Hi-C contact maps and fixed-cell imaging data.
• Validated the theory by comparing predicted two-point chromatin dynamics with experimental observations.

Main Results:

• The theory accurately forecasts experimentally observed two-point chromatin dynamics.
• Predicted rapid enhancer-promoter interactions and uncovered a scaling relationship between relaxation time and genomic separation.
• Showed that cohesin depletion accelerates diffusion but slows relaxation dynamics within topologically associating domains.

Conclusions:

• Chromatin dynamics can be reliably inferred from static structural data.
• 3D chromatin structure fundamentally governs dynamic behavior.
• The developed framework provides powerful tools for studying chromatin dynamics in various biological contexts.