The protein composition of the histone octamer is not uniform for all nucleosomes, as multiple variant isoforms exist of the core histone proteins, with variants of H2A and H3 being the most common (e.g., H2A.X and H2A.Z isoforms of H2A, H3.1 and H3.3 isoforms of H3). In addition, histone proteins can be chemically modified, with a prodigious variety of post-translational modifications occurring (acetylation, methylation, phosphorylation, ubiquitylation, and many more) at multiple residues in all of the histones (Tan et al. 2011). The enzymes responsible for these modifications are often highly residue-specific, as, for example, histone methyltransferases that modify lysine 4 on Histone 3 (H3K4) will not methylate nearby lysine residues (e.g., H3K9). These chemical modifications can alter the chemical and physical properties of the nucleosome but also serve to modulate binding by proteins that recognize the modified state (e.g., bind only to trimethylated H3K4) (Turner 1993; Jenuwein and Allis 2001). Thus, the beads on a string structure is not composed of uniform beads, as the chemical makeup of individual nucleosomes can, in principle, be extremely variable from nucleosome to nucleosome, with important consequences for genome function.
