The SAS3-dependent NuA3 histone acetyltransferase complex was originally 
identified on the basis of its ability to acetylate histone H3 in vitro. Whether 
NuA3 is capable of acetylating histones in vivo, or how the complex is targeted 
to the nucleosomes that it modifies, was unknown. To address this question, we 
asked whether NuA3 is associated with chromatin in vivo and how this association 
is regulated. With a chromatin pulldown assay, we found that NuA3 interacts with 
the histone H3 amino-terminal tail, and loss of the H3 tail recapitulates 
phenotypes associated with loss of SAS3. Moreover, mutation of histone H3 lysine 
14, the preferred site of acetylation by NuA3 in vitro, phenocopies a unique 
sas3Delta phenotype, suggesting that modification of this residue is important 
for NuA3 function. The interaction of NuA3 with chromatin is dependent on the 
Set1p and Set2p histone methyltransferases, as well as their substrates, histone 
H3 lysines 4 and 36, respectively. These results confirm that NuA3 is 
functioning as a histone acetyltransferase in vivo and that histone H3 
methylation provides a mark for the recruitment of NuA3 to nucleosomes.