HISTONE ACETYLATION AS AN EPIGENETIC DETERMINANT OF LONG-TERM TRANSCRIPTIONAL COMPETENCE

All four histones of the nucleosome core particle are subject to post- translational acetylation of selected lysine residues in their amino-t erminal domains. The modification is ubiquitous and frequent. Steady-s tate levels of acetylation have been shown to vary from one part of th e genome to another and to be maintained by a dynamic balance between the activities of two enzyme families, the histone acetyltransferases (HATs) and deacetylases (HDAs). The recent demonstration that some al least of these enzymes are homologous to, or identical with, known reg ulators of transcription, has renewed interest in the involvement of h istone acetylation in transcriptional control. Acetylation might influ ence the initiation and/or elongation phases of transcription in a chr omatin context, possibly by regulating the accessibility of nucleosoma l DNA to transcription factors or the displacement of histones by the progressing transcription complex. But there is also evidence to sugge st that acetylation might be involved in the longer-term regulation of transcription, acting as a marker by which states of genetic activity or inactivity are maintained from one cell generation to the next. Th is review outlines the evidence for such a role, using centric heteroc hromatin and the dosage-compensated male X chromosome in Drosophila as model systems, and suggests possible mechanisms by which it might ope rate.