Histone chaperones are a diverse group of proteins which facilitate nucleosome assembly/disassembly and interact with lysine acetyltransferases (KATs). The ability of histone chaperone Anti-silencing factor 1 (Asf1) to direct acetylation of lysine 56 of histone H3 (H3K56ac) represents an important regulatory step in genome replication and DNA repair. In Saccharomyces cerevisiae, Asf1 interacts functionally with a second chaperone, Vps75, and the lysine acetyltransferase (KAT) Rtt109. Both Asf1 and Vps75 can increase the specificity of histone acetylation by Rtt109, but neither alter selectivity on its own. However, changes in acetylation selectivity have been observed in histones extracted from cells, which contain a plethora of post-translational modifications. We have shown that histone chaperones are not only capable of activating KATs but can recognize specific acetylation patterns and direct crosstalk or secondary acetylation sites. Our proposed mechanism suggests that Gcn5 acetylates H3K14 on a nucleosome, recruiting remodeler complexes, allowing for the Asf1-H3K14ac/H4 complex to be acetylated at H3K56 by Rtt109-Vps75. This mechanism explains the conflicting biochemical data and the genetic links between Rtt109, Vps75, Gcn5 and Asf1 in the acetylation of H3K56. We are now exploring the ability of Rtt109-Vps75 to reassemble nucleosomes after acetylation.
