Post-Translational Modifications of Histones That Influence Nucleosome Dynamics

Nucleosomes are efficient DNA-packaging units. The fundamental protein unit of the nucleosome is the histone dimer, a simple α-helical domain possessing a highly basic, curved surface that closely matches the phosphate backbone of bent duplex DNA. Two copies each of histone heterodimer, H3/H4 and H2A/H2B, form a histone octamer that is wrapped with approximately 146 bp of duplex DNA in a left-handed spiral1,2 (Figure ​(Figure1).1). Through extensive electrostatic and hydrogen-bonding interactions, each histone dimer coordinates three consecutive minor grooves on the inner surface of the DNA spiral. The bending of DNA over the protein surface brings the phosphate backbone of the two strands closer together on the inside of the spiral, narrowing the major and minor grooves of DNA, while widening the grooves on the outside. This bent conformation of the DNA duplex, which would otherwise be energetically unfavorable, is maintained through charge neutralization from numerous arginine and lysine side chains of the histones. Open in a separate window Figure 1 Overview of nucleosome architecture. (A) Illustration of H2A/H2B and H3/H4 heterodimers and how they fit together to form the histone octamer. (B) Face and top view of the nucleosome structure. For this and all subsequent molecular representations of the nucleosome, the high-resolution crystal structure (PDB code 1KX5) was used.93