Untargeted tail acetylation of histones in chromatin: lessons from yeast

Dynamic acetylation of lysine residues in the amino-terminal tails of the core histones is functionally important for the regulation of diverse DNA-dependent processes in the nucleus, including replication, transcription, and DNA repair. The targeted and untargeted activities of histone lysine acetylases (KATs) and deacetylases (HDACs) both contribute to the dynamics of chromatin acetylation. While the mechanisms and functional consequences of targeted on histone acetylation are well understood, relatively little is known about untargeted histone acetylation. Here, we review the current understanding of the mechanisms by which untargeted KAT and HDAC activities modulate the acetylation state of nucleosomal histones, focusing on results obtained for H3 and H4 in budding yeast. We also highlight unresolved problems in this area, including the question of how a particular steady-state level of untargeted acetylation is set in the absence of cis-dependent mechanisms that instruct the activity of KATs and HDACs.