Diffusion-based DNA target colocalization by thermodynamic mechanisms

TL;DR

This paper presents a physics-based model showing that DNA target colocalization via diffusing molecules operates as a thermodynamic switch, requiring sufficient concentration and affinity for stable interactions, with implications for understanding passive diffusion mechanisms.

Contribution

It introduces a phase transition model explaining how passive diffusion mediates DNA colocalization, highlighting the threshold conditions for stable interactions.

Findings

Colocalization is a thermodynamic switch-like process.

Stable contacts depend on concentration and affinity thresholds.

Predictions on effects of genomic modifications on colocalization.

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.