A schematic summary of EPC1- and TIP60-dependent histone hyperacetylation during spermatid differentiation. Nuclei and apical regions closely associated with acrosome in round spermatids, elongating spermatids, and condensed spermatids are depicted. EPC1 and TIP60 accumulate at apical regions throughout this differentiation process. In round spermatids of steps 5 to 8, histones are major nuclear proteins but not hyperacetylated. The present study suggests that EPC1/TIP60 complexes likely mediate hyperacetylation of histones in elongating spermatids. Since EPC1 and TIP60 predominantly accumulate at apical regions near the acrosome, we speculate that EPC1/TIP60 complexes mediate acetylation of nonnucleosomal histones (indicated by a dotted blue arrow), which may in turn be incorporated into the chromatin (indicated by a red dotted arrow). Hyperacetylation of histones is shown to facilitate their subsequent replacement with TNPs and/or PRMs during elongating-to-condensing spermatid transition and/or in the elongating-spermatid stage.