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Histone H4 is one of the core components of the nucleosome, the basic building block of chromatin. Acetylation of histones is linked to a number of specific processes including transcriptional regulation and genomic organization. In yeast, acetylation of histone H3 at lysine 16 is required to maintain the boundaries between euchromatin (open and transcriptionally competent regions of chromatin) and heterochromatin (closed and transcriptionally inert). In Drosophila, lysine 16 acetylation is involved in the process of dosage compensation, the coordinate up-regulation of genes on the single male X chromosome that equalizes gene expression with that of genes on the two X chromosomes in females. In humans, the loss of lysine 16 acetylation appears to be a hallmark of specific types of cancer. Acetylation of lysine 16 inhibits the formation of higher order chromatin structure, suggesting that lysine 16 is a central regulator.