ROLES OF HISTONE ACETYLTRANSFERASES AND DEACETYLASES IN GENE-REGULATION

Acetylation of internal lysine residues of core histone N-terminal dom ains has been found correlatively associated with transcriptional acti vation in eukaryotes for more than three decades, Recent discoveries s howing that several transcriptional regulators possess intrinsic histo ne acetyltransferase (HAT) and deacetylase (HDAC) activities strongly suggest that histone acetylation and deacetylation each plays a causat ive role in regulating transcription. Intriguingly, several HATs have been shown an ability to acetylate nonhistone protein substrates (e.g. , transcription factors) in vitro as well, suggesting the possibility that internal lysine acetylation of multiple proteins exists as a rapi d and reversible regulatory mechanism much like protein phosphorylatio n. This article reviews recent developments in histone acetylation and transcriptional regulation. We also discuss several important, yet un answered, questions. BioEssays 20,615-626, 1998. (C) 1998 John Wiley & Sons, Inc.