Mechanics and Dynamics of X-Chromosome Pairing at X Inactivation

TL;DR

This study models the mechanical basis of X chromosome pairing during X inactivation, showing that specific DNA-binding molecules can induce pairing through a phase transition, aligning with experimental observations.

Contribution

We develop a statistical physics model demonstrating how molecular concentration thresholds induce X chromosome pairing via a phase transition, providing mechanistic insights.

Findings

Pairing occurs when molecular concentration exceeds a threshold.

Chromosome dynamics involve Brownian motion followed by recognition.

Model predictions align with experimental data on DNA modifications.

Abstract

At the onset of X Chromosomes Inactivation, the vital process whereby female mammal cells equalize X products with respect to males, the X chromosomes are colocalized along their Xic (X-Inactivation Center) regions. The mechanism inducing recognition and pairing of the X's remains, though, elusive. Starting from recent discoveries on the molecular factors and on the DNA sequences (the so-called ``pairing sites'') involved, we dissect the mechanical basis of Xic colocalization by using a Statistical Physics model. We show that soluble DNA specific binding molecules, as those experimentally identified, can be indeed sufficient to induce the spontaneous colocalization of the homologous chromosomes, but only when their concentration, or chemical affinity, rises above a threshold value, as a consequence of a thermodynamic phase transition. We derive the likelihood of pairing and its probability distribution. Chromosome dynamics has two stages: an initial independent Brownian diffusion followed, after a characteristic time scale, by recognition and pairing. Finally, we investigate the effects of DNA deletion/insertions in the region of pairing sites and compare model predictions to available experimental data.