A thermodynamic switch for chromosome colocalization - PubMed (original) (raw)

A thermodynamic switch for chromosome colocalization

Mario Nicodemi et al. Genetics. 2008 May.

Abstract

A general model for the early recognition and colocalization of homologous DNA sequences is proposed. We show, on thermodynamic grounds, how the distance between two homologous DNA sequences is spontaneously regulated by the concentration and affinity of diffusible mediators binding them, which act as a switch between two phases corresponding to independence or colocalization of pairing regions.

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Figures

F<sc>igure</sc> 1.—

Figure 1.—

Pictures of typical configurations, from computer simulations, of the model system at thermodynamic equilibrium, in the two described phases discussed in Figure 2 (A, independent motion; C, colocalization) and their intermediate crossover region (B), for the shown values of the concentration of molecular mediators, c (here EX = 1.2_kT_).

F<sc>igure</sc> 2.—

Figure 2.—

(Top) The equilibrium chromosome average square distance, d_2, is shown as a function of the concentration of binding molecules, c (here the molecule/chromosome affinity is EX = 1.2_kT): for formula image, _d_2 approaches values as big as the system size and chromosomes are randomly and independently diffusing (horizontal dotted lines give the values found for pure random walks); for c > _c_tr, _d_2 rapidly decays to zero, showing that they have colocalized. Around _c_tr there is a crossover regime, approximately between _c_1 and _c_2, where chromosomes tend to align since _d_2 is smaller than in the region where they move independently, but its fluctuations, Δ_d_2, are of the order of _d_2; here chromosomes are only transiently colocalizing. (Bottom) A similar behavior is found when _d_2 is plotted as a function of the chemical affinity, EX, shown here for c = 0.1%.

F<sc>igure</sc> 2.—

Figure 2.—

(Top) The equilibrium chromosome average square distance, d_2, is shown as a function of the concentration of binding molecules, c (here the molecule/chromosome affinity is EX = 1.2_kT): for formula image, _d_2 approaches values as big as the system size and chromosomes are randomly and independently diffusing (horizontal dotted lines give the values found for pure random walks); for c > _c_tr, _d_2 rapidly decays to zero, showing that they have colocalized. Around _c_tr there is a crossover regime, approximately between _c_1 and _c_2, where chromosomes tend to align since _d_2 is smaller than in the region where they move independently, but its fluctuations, Δ_d_2, are of the order of _d_2; here chromosomes are only transiently colocalizing. (Bottom) A similar behavior is found when _d_2 is plotted as a function of the chemical affinity, EX, shown here for c = 0.1%.

F<sc>igure</sc> 3.—

Figure 3.—

This phase diagram shows the state of the two chromosomes at thermodynamic equilibrium in a range of values of chemical affinity and concentration of their molecular mediators, i.e., in the (EX, c) plane. For small EX and c, chromosomes move independently while, above a transition region, they spontaneously colocalize. The transition line, _c_tr(EX), is marked by the thick black line. Colocalization, thus, can be spontaneously attained by upregulation of mediator concentration, c, or of molecule chemical affinity, EX, to chromosomal sequences.

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