Notably, neither Sas2 nor Esa1 can acetylate nucleosomal histones "in vitro" as a free enzyme. Such complexes acetylate histone tails to activate genes. Sas2 is also observed to acetylate H3K14 "in vitro" on free histones. Gcn5 cannot acetylate nucleosomal histones in the absence of other protein factors. Aspirin is able to acetylate several other targets in addition to COX isoenzymes. Gcn5 has been shown to acetylate substrates when it is part of a complex. These HATs are known to acetylate all of the histone subunits in the nucleosome.