Cryo-EM structures of the human SIN3B histone deacetylase complex unveils assembly, enzymatic activation and histone lysine selection mechanisms

Lysine acetylation is a key transcriptional activating signalling modification occurring at the flexible ends of the histone proteins within the nucleosome, which is the basic unit of chromatin. Several histone deacetylase complexes in human fine tune these modifications thereby regulating the transcriptional output of each gene. Although histone deacetylase complexes are crucial in defining transcriptional programs during cell differentiation and cell cycle the structural information and mechanisms of actions of these holoenzymes is poor. Here we present the structure of the SIN3B histone deacetylase complex in apo form and in complex with an acetyl-lysine mimic compound, showing insights into its subunit architecture, catalytic regulation, substrate recognition and targeting to cell cycle genes.