Updated FTP location. p300 is a histone acetyltransferase that associates with crucial biological processes. p300 acetylates all four histones in the nucleosome, a basic unit of chromatin, and alters chromatin structure and dynamics. In this study, we performed structural and biochemical analysis to understand the nucleosome binding by p300. Crosslinking mass spectrometry suggests that the p300 catalytic core binds to nucleosomes in multiple binding forms to acetylate different histone tails.