Stochastic motion and transcriptional dynamics of distal enhancer-promoter pairs on a compacted chromosome.

Chromosomes in the eukaryotic nucleus are highly compacted, with a crowded polymer organization of fractal dimension three. However, for many functional processes, including transcription initiation, the 3D pair-wise motion of distal chromosomal elements, such as enhancers and promoters, is essential and necessitates dynamic fluidity. Therefore the interplay of chromosome organization and dynamics is crucial for gene regulation. Here, we use a live imaging assay to simultaneously measure the positions of pairs of enhancers and promoters and their transcriptional output in the developing fly embryo while systematically varying the genomic separation between these two DNA elements. Our analysis reveals a combination of a compact globular organization with fast subdiffusive dynamics. These combined features cause an anomalous scaling of polymer relaxation times with genomic separation and lead to long-ranged correlations compared to existing polymer models. This scaling implies that enhancer-promoter encounter times are much less dependent on genomic distance than predicted by existing polymer models, with potentially significant consequences for eukaryotic gene expression.