Large-­Scale Structural Transitions in Supercoiled DNA Revealed By Coarse­-Grained Simulation

Topological constraints, such as those associated with DNA supercoiling, play an integral role in genomic regulation and organization in living systems. However, physical understanding of the principles that underlie DNA structure and organization at biologically-relevant length-scales remains a formidable challenge. We develop a coarse-grained simulation approach for predicting equilibrium conformations of supercoiled DNA. With this approach, we study the conformational transitions that arise due to supercoiling across the full range of supercoiling densities that are commonly explored by living systems. Simulations of ring DNA molecules with lengths up to the scale of topological domains in the Escherichia coli chromosome (~ 10 kilobases) reveal large-scale structural transitions elicited by supercoiling. The structural transitions result in 3 supercoiling conformational regimes that are governed by a competition between chiral coils, extended plectonemes, and branched hyper-supercoils. We find that these conformational transitions exert a pronounced effect on the looping probability of genomically distal elements, and we consider the consequences of these effects on regulation of the genome by distal regulatory elements. The length-scales and supercoiling regimes investigated here coincide with those relevant to transcription-coupled remodeling of supercoiled topological domains, and we discuss possible implications of these findings in terms of the interplay between transcription and topology in bacterial chromosome organization.