Effect of acetylation on the binding of N-terminal peptides of histone H4 to DNA

Abstract

The trypsin-sensitive N-terminal domain of histone H4 (residues 1-19) contains four acetylation sites at residues 5, 8, 12 and 16 and may play a separate role in chromatin structure from the remainder of the H4 chain. High-resolution proton NMR has been used to probe the DNA-binding of this H4 domain using the peptides (4-17), (1-23) and (1-37). Binding strength is in the order (1-37) greater than (1-23) greater than (4-17) but is weak even for (1-37). The observed weak binding correlates with arginine rather than lysine content and marked changes in the glycine resonance indicate the involvement of the peptide backbone in binding. When peptides (1-23) and (4-17) are fully acetylated with acetic anhydride, this weak binding is totally abolished. Circular dichroism indicates that neither acetylated nor unacetylated peptides take up any secondary structure. The results are consistent with the view that acetylation of H4 in vivo lifts the N-terminal domain off the DNA and thereby promulgates a major structural change in the chromatin.