Histone acetylation and control of gene expression

The post-translational acetylation of the core histories was first recognised more than a quarter of a century ago (Allfrey et al. 1964). Since then, considerable research effort has been expended in attempting to reveal the mechanisms by which acetylation is controlled and, most importantly, its functional significance. The reasons for the interest in this phenomenon are not hard to find. The intimate association of histones with cellular DNA and their extreme conservation through evolution both make it likely that any change in their structure, particularly one that involves a change in net charge, will have an effect on chromatin function. Thus, as frequently stated in introductory paragraphs, histone acetylation is potentially a major influence on events such as transcription, replication, DNA packaging through the cell cycle and DNA repair. However, despite the conceptual appeal of such a central role, definitive evidence is lacking and we have intriguing correlations rather than experimental data on which detailed molecular mechanisms can be based. Indeed, belief in the functional importance of histone acetylation has tended to rely on evolutionary arguments of the sort used to explain the popularity of sexual reproduction in the animal kingdom, namely: In evolutionary terms sexual reproduction must be important since so many species devote so much energy to it' (Leakey, 1976).