Nucleosomes are octomers of associated dimers of histone H3 and H4 proteins capped by dimers of H2A and H2B, and this protein core is surrounded by ∼147 bp of double-stranded DNA. The physical spacing between repeating nucleosomal subunits controls the level of DNA condensation and the access of transcription factors and replication machinery to the genetic information. Post-translational modifications to the flexible N-terminal tails that protrude from the nucleosomal core controls the level of DNA packaging, and influences the temporal and spatial expression of genes. The most commonly studied modifications are the acteylation of lysine, which is ‘written’ and ‘erased’ by histone acetyltransferases and histone deacetylases, and lysine methylation which is ‘written’ and ‘erased’ by protein methyltransferases and protein demethylases. The marks are ‘read’ by two major families of proteins: Bromodomains bind to and recognize acetylated lysine, while the Royal family of proteins recognize and bind to methylated lysine. Other important histone post-translational modifications include the methylation of arginine, phosphorylation, and ubiquitination.