Fig. 5: Model of SIN3B function at gene promoters.

a, b Schematic cartoon illustrating a model for the function of SIN3B complex at target genes. SIN3B counteract p300-mediated acetylation. p300 binds the NF-Y sequence at target genes, whereas p300 can be recruited by various transcription factors (TFs) and their DNA-specific sequence (indicated with a white box). The HDAC active site is indicated with a star. The conformational change of the SIN3B^{Gate loop} upon histone H3 tail binding is indicated. H3K27/K18/K14 (and not H3K9) are main acetylation targets by p300^52,56. c overall structure of SIN3B complex is shown in cartoon and transparent surface representation. d Modelling of the H3 histone tail based on the structure of BHC80^PHD:H3 (PDB ID: 2PUY) superposed to our SIN3B structure (PHD1 as a reference) and based on our SIN3B:SAHA structure. Lysine residues on the H3 N-terminus are shown, K9 would be too far from the catalytic site, lysine residues more C-terminal to H3 residue 13 (i.e. K14, K18 and K27) would be able to enter the HDAC catalytic site. e–h Deacetylation reactions by the SIN3B complex of nucleosomes with the acetyl moiety localised in different positions along the H3 histone tail (i.e. H3K9ac, H3K14ac and H3K27ac). The H3K27/K14 deacetylation experiments are also performed with a SIN3B PHF12 PHD finger 1 mutant (SIN3B^PHF12D57A) complex, and the H3K27 deacetylation experiment is also performed with the HDAC2 apo enzyme. Quantifications from western blot data (performed in triplicate and one replicate per experiment are shown in e–g) are plotted in (h). Data are presented as mean values ± S.D. of independent experiments, n = 3.