Histone acetylation as an epigenetic determinant of long-term transcriptional competence

Abstract.

All four histones of the nucleosome core particle are subject to post-translational acetylation of selected lysine residues in their amino-terminal domains. The modification is ubiquitous and frequent. Steady-state levels of acetylation have been shown to vary from one part of the 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 at least of these enzymes are homologous to, or identical with, known regulators of transcription, has renewed interest in the involvement of histone acetylation in transcriptional control. Acetylation might influence the initiation and/or elongation phases of transcription in a chromatin context, possibly by regulating the accessibility of nucleosomal DNA to transcription factors or the displacement of histones by the progressing transcription complex. But there is also evidence to suggest 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. This review outlines the evidence for such a role, using centric heterochromatin and the dosage-compensated male X chromosome in Drosophila as model systems, and suggests possible mechanisms by which it might operate.