DNA geometry around highly transcribed bacterial genes

Abstract

Recent high-resolution (500 bp) Hi-C experiments reported contact maps with unusual patterns around highly expressed bacterial DNA loci. These patterns, described as arched stripes and bundled domains, extend over nearly 100 kbp. We performed Brownian Dynamics simulations with a specially designed coarse-grained model to rationalize these findings. The main feature of the model is that it takes explicitly into account the waves of positive (respectively, negative) supercoiling generated by the translocating polymerase downstream (respectively, upstream) of its position. Contact maps computed from the simulations also display the arched stripe and bundled domain patterns for above-threshold values of the rate of twist injection. Computed DNA conformations indicate that these patterns reflect an extraordinarily entangled DNA geometry, which involves both plectonemic and toroidal supercoiling, with some DNA segments experiencing both of them simultaneously. Moreover, DNA segments located on each side of the polymerase systematically wind around tracts located on the other side, which is a purely out-of-equilibrium effect driven by the continuous injection of twist. The present work therefore reveals that repeated transcription of a DNA locus systematically brings into contact DNA segments separated by several tens of kbp, which may eventually contribute to allosteric modulation and long-range communication.