Histone acetylation increases the solubility of chromatin and occurs sequentially over most of the chromatin. A novel model for the biological role of histone acetylation

Abstract

The effect of histone acetylation on chromatin solubility has been studied. Nucleosome cores are fairly soluble over a range of Mg2+ and Na+ concentrations. Increasing the amount of Na+ relative to a fixed concentration of Mg2+ leads to increased solubility. Although the effect is not large, acetylated cores are more soluble than control cores, all other factors being equal. Acetylated oligonucleosomes are vastly more soluble than control oligonucleosomes with the greatest differential seen in the presence of Mg2+ at low ionic strengths. Solubility of acetylated oligonucleosomes is favored when the majority of the histones in the nucleosomes are all highly acetylated. Contiguous highly acetylated nucleosomes are enriched in the rapid kinetic form of histone acetylation after short term exposure to butyrate. These observations have been exploited in a fractionation scheme for chromatin based on the levels of hyperacetylation attained after varied times of exposure to sodium butyrate. Essentially all DNA sequences in an unsynchronized cell population are associated with rapidly acetylated histones. Since it is highly unlikely that each cell has its own discrete set of sequences bound to acetylated histone and since the amount of rapidly acetylated histone in a single cell is relatively small (approximately 10% of total histone), we surmise that rapid acetylation migrates throughout much of the chromatin, perhaps in a sequential and highly organized manner. We postulate that the biological role of histone acetylation is to provide a means for sequentially exposing the entire chromatin for surveillance for DNA damage and possibly for recognition of different regions of the DNA by specific (regulatory?) proteins.