Overlapping but distinct patterns of histone acetylation by the human coactivators p300 and PCAF within nucleosomal substrates

A number of transcriptional coactivators possess intrinsic histone acetylas e activity, providing a direct link between hyperacetylated chromatin and t ranscriptional activation. We have determined the core histone residues ace tylated in vitro by recombinant p300 and PCAF within mononucleosomes. p300 specifically acetylates all sites of histones H2A and H2B known to be acety lated in bulk chromatin in vivo but preferentially acetylates lysines 14 an d 18 of histone H3 and lysines 5 and 18 of histone H4. PCAF primarily acety lates lysine 14 of H3 but also less efficiently acetylates lysine 8 of H4. PCAF in its native form, which is present in a stable multimeric protein co mplex lacking p300/CBP, primarily acetylates H3 to a monoacetylated form, s uggesting that PCAF-associated polypeptides do not alter the substrate spec ificity. These distinct patterns of acetylation by the p300 and PCAF may co ntribute to their differential roles in transcriptional regulation.