Diffusion-based DNA target colocalization by thermodynamic mechanisms

Abstract

In eukaryotic cell nuclei, a variety of DNA interactions with nuclear elements occur, which, in combination with intra- and inter-chromosomal cross-talks, shape a functional 3D architecture. In some cases they are organized by active, i.e. actin/myosin, motors. More often, however, they have been related to passive diffusion mechanisms. Yet, the crucial questions on how DNA loci recognize their target and are reliably shuttled to their destination by Brownian diffusion are still open. Here, we complement the current experimental scenario by considering a physics model, in which the interaction between distant loci is mediated by diffusing bridging molecules. We show that, in such a system, the mechanism underlying target recognition and colocalization is a thermodynamic switch-like process (a phase transition) that only occurs if the concentration and affinity of binding molecules is above a threshold, or else stable contacts are not possible. We also briefly discuss the kinetics of this `passive-shuttling' process, as produced by random diffusion of DNA loci and their binders, and derive predictions based on the effects of genomic modifications and deletions.