The packaging of DNA into chromatin is an important regulator of transcription. This regulation may operate either by short-term switching of the transcription of specific genes or by packaging chromosome domains into structures that either facilitate or repress the potential for gene expression. Such packaging may occur during chromatin assembly through S-phase of the cell cycle. Recent evidence shows that the post-translational acetylation of histones of the nucleosome core particle is intimately involved in all these processes. New approaches allowing exploration of the molecular details, the functional effects and the regulation of histone acetylation promise to reveal new mechanisms of genomic regulation.