Although the nucleosome in its role as the fundamental structural unit of eukaryotic chromatin has been with us for many years, mysteries remain. Prominent among them is the long standing observation that the amino terminal tails of the eight histones comprising the nucleosome core particle are all subject to various, enzyme-catalyzed, posttranslational modifications (Wu et al., 1984). What benefit does the cell gain by expending energy in subjecting a highly conserved structural component to such a bewildering array of acetylations, phosphorylations, ADP-ribosylations etc?

Of the various modifications to which histones are subject, acetylation of lysine residues is the most extensively studied. Levels of histone acetylation are generally higher in transcriptionally active than in quiescent chromatin (eg Hebbes et al., 1992, reviewed by Turner, 1991), an association that is only consistently true for this post-translational modification. Histone acetylation could influence transcription at several stages, for example, by causing transcription factors to bind or by inducing structural transitions in chromatin during initiation or by facilitating histone displacement and repositioning during polymerase elongation. Any or all of these effects (and others) are possible. But at this stage, rather than considering the different possible functional consequences of acetylation, the mechanisms responsible for these effects will be discussed. They can be grouped into just two general, and not mutually exclusive categories. The first contains mechanisms in which histone acetylation itself changes the structure of chromatin, thereby exerting a direct functional effect. The second contains mechanisms in which histone acetylation does not necessarily change nucleosome structure but instead generates new sites on the surface of the nucleosome to which functionally significant non-histone proteins can attach, thereby exercising an indirect effect.