Fig 1: HDAC1 modulates OGG1 activity.a, b Representative images and quantification of OGG1 acetylation assessed by western blot analysis using antibody against acetylated lysine (Ac-Lysine, 4G12). Recombinant OGG1 (100 ng) was first acetylated by p300 (25 ng), and then incubated with titrated amount of HDAC1 (25 and 50 ng). a, b Four replicates from four independent experiments. c Reaction scheme of OGG1 cleavage assay. 5'IRDye800CW-labeled oligonucleotides (33 nt) that contain an 8-oxoG base at position 17 and complementary unlabeled strand were used as OGG1 substrate. Recombinant OGG1 proteins were incubated with OGG1 substrate and resolved by 20% denaturing urea PAGE. d, e Representative images and quantification of OGG1 cleavage activity on the reaction samples shown in Fig. 3a. d, e Seven replicates from four independent experiments. Nuclear extracts from HEK cells overexpressing OGG1 were used as a positive control. f Co-immunoprecipitation of OGG1 with HDAC1 in cortical nuclear extracts from 2-month-old wild-type mice (n = 2) from one experiment. The asterisks indicate the nonspecific cross-reaction with the IgG heavy and light chains. g, h Representative images and quantification of acetylation status of endogenous OGG1 in hippocampal lysates of 13M control (n = 4) and Hdac1 cKO (n = 4) animals. g, h Two independent experiments. i Representative images of OGG1 cleavage assay using hippocampal nuclear extracts of 13M control and Hdac1 cKO mice. j Quantification of cleaved 17-nt products after OGG1 cleavage assay using hippocampal nuclear extracts of 13M control (n = 6) and Hdac1 cKO (n = 4) animals. i, j Two independent experiments. All values are shown as mean ± SEM. Statistical analysis: b, e one-way ANOVA with Tukey’s post hoc test; h, j two-tailed Student’s t test. Source data are provided as a Source Data file.
Fig 2: Chemical structures of histone acetyltransferases (HAT) inhibitory N-phenyl (PU139) and N-benzyl (PU141) pyridoisothiazolones and in vitro inhibition of HATs in biochemical assays. Blue lines with diamonds represent inhibition of CBP, olive lines with circles p300, red lines with squares Gcn5 and orange lines with triangles PCAF. The IC50 values have been presented in a tabulated version in the literature.61
Supplier Page from BPS Bioscience, Inc. for p300 (KAT3B), His-GST-tag Recombinant