Static Three-Dimensional Structures Determine Fast Dynamics Between Distal Loci Pairs in Interphase Chromosomes

TL;DR

This paper presents a theory that predicts chromatin dynamics from static 3D structures derived from Hi-C data, explaining rapid enhancer-promoter interactions and the influence of cohesin on chromatin mobility.

Contribution

The authors develop a novel framework linking static 3D chromatin structures to dynamic behavior, enabling accurate predictions of chromatin motion from static data.

Findings

Predicts rapid enhancer-promoter interactions

Uncovers a scaling law between relaxation time and genomic separation

Shows cohesin depletion affects diffusion and relaxation dynamics

Abstract

Live-cell imaging experiments have shown that the distal dynamics between enhancers and promoters are unexpectedly rapid and incompatible with standard polymer models. The discordance between the compact static chromatin organization and dynamics is a conundrum that violates the expected structure-function relationship. We developed a theory to predict chromatin dynamics by accurately determining three-dimensional (3D) structures from static Hi-C contact maps or fixed-cell imaging data. Using the calculated 3D coordinates, the theory accurately forecasts experimentally observed two-point chromatin dynamics. It predicts rapid enhancer-promoter interactions and uncovers a scaling relationship between two-point relaxation time and genomic separation, closely matching recent measurements. The theory predicts that cohesin depletion accelerates single-locus diffusion while significantly slowing relaxation dynamics within topologically associating domains (TADs). Our results demonstrate that chromatin dynamics can be reliably inferred from static structural data, reinforcing the notion that 3D chromatin structure governs dynamic behavior. This general framework offers powerful tools for exploring chromatin dynamics across diverse biological contexts.