A decade of histone acetylation: Marking eukaryotic chromosomes with specific codes

Post-translational modification of histones, a major protein component of eukaryotic chromosomes, contributes to the epigenetic regulation of gene expression. Distinct patterns of histone modification are observed at specific chromosomal regions and affect various reactions on chromosomes (transcription, replication, repair, and recombination). Histone modification has long been proposed to have a profound effect on eukaryotic gene expression since its discovery in 1964. Verification of this idea, however, was difficult until the identification of enzymes responsible for histone modifications. Ten years ago (1995), histone acetyltransferases (HATs), which acetylate lysine residues in histone amino-terminal tail regions, were isolated. HATs are involved in the regulation of both promoter-specific transcription and long-range/chromosome-wide transcription. Analyses of HATs and other modification enzymes have revealed mechanisms of epigenetic regulation that are mediated by post-translational modifications of histones. Here we review some major advances in the field, with emphasis on the lysine specificity of the acetylation reaction and on the regulation of gene expression over broad regions.