Condensation of chromatin: role of multivalent cations.

We have used electric dichroism to investigate the influence of multivalent cations upon the compaction of chicken erythrocyte chromatin from the unfolded, 10-nm fiber to the 30-nm solenoid and subsequent aggregation. The pattern of condensation, which consists of compaction plus aggregation, is found to be strikingly similar for a variety of cations of differing charge, including the physiologically important polyamines spermine and spermidine. With a few exceptions such as Cu2+ and Gd3+, an optimally compacted fiber with reproducible hydrodynamic properties is produced prior to the onset of aggregation. We report the concentrations of di-, tri-, and tetravalent cations required for optimal condensation; in addition, for tri- and tetravalent cations, we were able to estimate the extent of charge neutralization produced by their binding to the optimally compacted fiber. The results show that the multivalent ion concentration required for optimal compaction decreases as cationic charge increases. In addition, the effect of a mixture of dilute mono- and multivalent cations on chromatin condensation is synergistic, rather than competitive as has been found for the multivalent cation induced condensation of DNA or the B----Z conformational transition. A simple calculation indicates that the entropy of ion uptake in chromatin condensation is surprisingly constant for a range of ionic conditions; this factor may be a dominant one in determining the folding equilibrium.