Understanding histone acetyltransferase Rtt109 structure and function: how many chaperones does it take?

► Histone chaperones Vps75 and Asf1 stimulate Rtt109 acetyltransferase toward histone H3 approximately 100-fold. ► Rtt109-Asf1 acetylates H3 K56, while Rtt109-Vps75 acetylates H3 K9 and K27. ► Auto-acetylation of Rtt109 at K290 is essential and is not influenced by Vps75. ► Based on structural work, the stoichiometry of Vps75-Rtt109 is uncertain; it may be 2:1 or 2:2. ► Vps75 imports Rtt109 into the nucleus, stabilizes Rtt109, and positions H3 for acetylation by Rtt109.