Phase transitions in nuclei and chromatin

Changes in the volume of rat liver nuclei have been monitored as a function of modifications in ionic environment (from 0 to 20 mM), temperature (from 4 to 37°C) and pH (from 1 to 8). An abrupt reduction of nuclear volume occurred with increasing ion concentration, this contraction being more pronounced with bivalent (either Ca²⁺ or Mg²⁺) than with monovalent (either Na⁺ or K⁺) cations. The lowering of pH produced a similar effect. Parallel changes in chromatin structure took place at the same time as phase-like transitions. Atomic absorption spectroscopy allowed determination of free and nuclei-bound ions, pointing to the presence of a sizeable number of free binding sites for chromatin-DNA even within intact nuclei. DNA-phosphate sites appear to be neutralized by ions strictly according to the size of the electric charge and polyelectrolyte theory. Partial digestion (by micrococcal nuclease) or simple breaks (by chemical carcinogens) of the chromatin-DNA fiber caused respectively elimination or reduction of the abrupt volume changes in the intact nuclei. The apparent role of chromatin structure versus nuclear matrix in determining the shape and volume of intact nuclei is briefly discussed.