Spatially correlated motion controls chromosomal locus pair encounter dynamics

Spatial encounters between pairs of genomically distant DNA loci are critical for the initiation of transcription in eukaryotes. However, while the three-dimensional structure of the chromosome is increasingly well characterized, the physical principles governing the real-time dynamics of locus pairs remain poorly understood. Based on recent data sets from imaging experiments, we show that locus-pair distances diffuse anomalously slowly. Combining stochastic trajectory analysis and polymer simulations, we show that these slow diffusivities can be explained by spatial correlations of locus fluctuations within the nucleus, leading to slower relative motion as loci approach each other. Our analysis reveals such correlations in experimental locus pair tracking data from both fly and mouse cells, and even after degradation of loop extrusion factors. At the functional level, our model predicts that spatial correlations control a non-trivial trade-off between pairwise encounter frequencies and durations, with key consequences for transcriptional activation and gene regulation.