Epigenetic mechanisms to propagate histone acetylation by p300/CBP

Abstract

Histone acetylation is important for the activation of gene transcription but little is known 14 about its direct ‘read/write’ mechanisms. Here, we report cryo-electron microscopy structures 15 in which a p300/CBP multidomain monomer recognizes histone H4 N-terminal tail (NT) 16 acetylation (ac) in a nucleosome and acetylates non-H4 histone NTs within the same 17 nucleosome. p300/CBP not only recognized H4NTac via the bromodomain pocket 18 responsible for ‘reading’, but also interacted with the DNA minor grooves via the outside of 19 that pocket. This directed the catalytic center of p300/CBP to one of the non-H4 histone NTs. 20 The primary target that p300 ‘writes’ by ‘reading’ H4NTac was H2BNT, and H2BNTac 21 promoted H2A-H2B dissociation from the nucleosome.