Interaction between N-terminal domain of H4 and DNA is regulated by the acetylation degree.

To study whether the acetylation of one or more of the four acetylatable lysines of histone H4 affects its binding to DNA, we have designed a protection experiment with a model system consisting in phage lambda DNA as substrate, StuI as restriction endonuclease and histone H4 with different degrees of acetylation as the protective agent. It can be deduced from the experimental data that the protection afforded by the histone is not dependent on the number of positive charges lost by acetylation. Thus, non-acetylated H4 and mono-acetylated H4 cause similar protection, while di-acetylation of the histone seems to be the crucial step in significantly weakening the interaction between H4 and DNA. This is confirmed by the results obtained in protection experiments carried out using H4 peptide (1-24) with different degrees of acetylation as the protecting agent. As restriction enzyme can imitate any trans-acting factor with sequence recognition, the di-acetylated isoform of histone H4 can be the starting point, through acetylation, to unmask DNA sequences, allowing the accessibility of regulatory factors to DNA in the chromatin.