Abstract: Histone acetyltransferases and deacetylases with specificities for different sites of acetylation affect common chromatin regions. This could generate unique patterns of acetylation that may specify downstream biological processes. To search for existence of these patterns and their relationship to gene activity, we analyzed the genome-wide acetylation profiles for eleven lysines in the four core histones of Saccharomyces cerevisiae. We find that both hyper- and hypoacetylation of individual lysines are associated with transcription, generating distinct patterns of acetylation that define groups of biologically related genes. The genes within these groups are significantly coexpressed, mediate similar physiological processes, share unique cis-regulatory DNA motifs, and are enriched for binding of specific transcription factors. Our data also indicate that the in vivo binding of the transcription factor Bdf1 is associated with acetylation on most lysines but relative deacetylation on H4 lysine 16. Thus, certain acetylation patterns may be used as surfaces for specific protein-histone interactions, providing one mechanism for coordinate regulation of chromatin processes that are biologically related.