The silence of the chromosomes

Credit: SCIENCE PHOTO LIBRARY

In most mammals, males carry a pair of sex chromosomes designated 'XY', females carry 'XX' (pictured). Only one X chromosome per cell is needed for healthy development, and in females one of the pair of X chromosomes has to be silenced, that is, its gene expression switched off. Writing in Physical Review Letters, Mario Nicodemi and Antonella Prisco recognize this as a symmetry-breaking problem — how does a cell 'decide' which of the two chromosomes to silence? — and take a statistical-mechanics approach to solving it (Phys. Rev. Lett. 98, 108104; 2007).

Genetic studies have shown how the silencing itself works: each X chromosome includes a gene known as Xist, and RNA expressed from this gene shuts off further gene expression from the chromosome. Somehow, on one of the chromosomes but not the other, Xist is blocked and gene expression continues as normal. Nicodemi and Prisco consider how a blocking factor (perhaps an aggregate of proteins) could develop and then bind to one of the chromosomes, breaking the symmetry and protecting that chromosome from Xist.

In their model, particles (representing the likely components of the blocking factor) diffuse between points on a lattice that surrounds two parallel segments representing the X chromosomes. Interactions between particles and their nearest neighbours are described using an effective energy of either E₀ = 2.4kT, equivalent to a weak hydrogen bond at room temperature, or E₀ = 0, which describes a random walk. Similarly, the binding energy at lattice sites associated with the chromosomes is set to E_X = 2.4kT.

In the case of the random walk, Monte Carlo simulations show that there is no clustering of particles; but for E₀ = 2.4kT, there is. In a trade-off between energy and entropy, the clusters eventually build into a single complex around one of the chromosomes — breaking the symmetry of the system. The timescale of the process is determined by how close together the segments of the two chromosomes are: their observed proximity during silencing in biological systems could be necessary to be able to achieve the assembly of a blocking factor quickly enough.

As the authors point out, E_X might not have the same value for each chromosome, due to copying errors during DNA replication. Then the symmetry is already broken, the chromosome with higher affinity will attract the blocking factor and save itself from silencing.