Catalytic component of the NuA4 histone acetyltransferase (HAT) complex which is involved in epigenetic transcriptional activation of selected genes principally by acetylation of nucleosomal histones H4, H3, H2B, H2A and H2A variant H2A.Z (By similarity). Acetylates histone H4 to form H4K5ac, H4K8ac, H4K12ac and H4K16ac, histone H3 to form H3K14ac, and histone H2A to form H2AK4ac and H2AK7ac (By similarity). The NuA4 complex is involved in the DNA damage response and is required for chromosome segregation. The NuA4 complex plays a direct role in repair of DNA double-strand breaks (DSBs) through homologous recombination (By similarity). Recruitment to promoters depends on H3K4me. Also acetylates non-histone proteins (By similarity). In addition to protein acetyltransferase, can use different acyl-CoA substrates, such as 2-hydroxyisobutanoyl-CoA (2-hydroxyisobutyryl-CoA) or (2E)-butenoyl-CoA (crotonyl-CoA), and is able to mediate protein 2-hydroxyisobutyrylation and crotonylation, respectively (By similarity). acetyl-CoA + L-lysyl-[histone] = CoA + H(+) + N(6)-acetyl-L-lysyl-[histone] acetyl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-acetyl-L-lysyl-[protein] 2-hydroxyisobutanoyl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-(2-hydroxyisobutanoyl)-L-lysyl-[protein] (2E)-butenoyl-CoA + L-lysyl-[protein] = CoA + H(+) + N(6)-(2E)-butenoyl-L-lysyl-[protein] Component of the NuA4 histone acetyltransferase complex. Following DNA damage, localizes to sites of DNA damage, such as double stand breaks (DSBs). The ESA1-RPD3 motif is common to ESA1 and RPD3 and is required for ESA1 histone acetyl-transferase (HAT) activity and RPD3 histone deacetylase (HDAC) activity. Autoacetylation at Lys-296 is required for proper function. Belongs to the MYST (SAS/MOZ) family.