A Symmetry Breaking Model for X Chromosome Inactivation

TL;DR

This paper introduces a statistical mechanics model explaining how cells randomly inactivate one X chromosome in mammals, highlighting the role of symmetry breaking and colocalization in the process.

Contribution

The model provides a novel explanation for the symmetry breaking mechanism in X chromosome inactivation, supported by simulations and experimental data comparison.

Findings

Self-assembly of a blocking factor complex causes symmetry breaking.

Only one blocking factor complex forms out of many molecules.

Colocalization is crucial for the initiation of X-inactivation.

Abstract

In mammals, dosage compensation of X linked genes in female cells is achieved by inactivation of one of their two X chromosomes which is randomly chosen. The earliest steps in X-inactivation (XCI), namely the mechanism whereby cells count their X chromosomes and choose between two equivalent X, remain mysterious. Starting from the recent discovery of X chromosome colocalization at the onset of X-inactivation, we propose a Statistical Mechanics model of XCI, which is investigated by computer simulations and checked against experimental data. Our model describes how a `blocking factor' complex is self-assembled and why only one is formed out of many diffusible molecules, resulting in a spontaneous symmetry breaking (SB) in the binding to two identical chromosomes. These results are used to derive a scenario of biological implications describing all current experimental evidences, e.g., the importance of colocalization.