Fig 1: Loss of Kat2a depletes H3K9ac and perturbs transcription factor-binding in a subset of regulatory gene promoters.(A) Quantification of H3K9ac and H3K27ac ChIPseq peaks at H3K4me3 gene promoters in Kat2a WT and KO primary MLL-AF9 leukemias. (B) Top ENCODE ChIP-seq Significance Tool enrichments for H3K9ac-positive promoters exclusive to Kat2a WT primary MLL-AF9 leukemia cells. These promoters constitute Kat2a acetylation targets. (C) Distribution of burst frequencies for Kat2a acetylation targets vs. non-targets within the 2588-Robust gene set. Values as calculated by D3E with 2585 genes called differential. Mann-Whitney non-parametric test for comparison of rank medians; p<0.0001 for Kat2a WT vs. KO comparisons. WT vs KO median rank differential non-significant. (D) Distribution of burst frequencies for Kat2a acetylation targets vs. non-targets amongst cells in cluster 7; 857 genes considered as used in RACE-ID. Burst frequencies were calculated by D3E, with 332 genes called differential. Mann-Whitney non-parametric test for comparison of rank medians; p<0.001 for Kat2a WT vs. KO comparisons. (E) ChIP-quantitative PCR analysis of Myc binding in selected Kat2a acetylation target promoter peaks; mean values for 2–4 independent experiments using pooled BM or Spleen of Kat2a WT vs KO MLL-AF9 secondary leukemias. Mean enrichments: WT = 2.158, KO = 1.357, 95% CI of difference 0.01273 to 1.589; 2-way ANOVA p<0.05 for genotype contribution. (F) ChIP-quantitative PCR analysis of Gabpa binding in selected Kat2a acetylation target promoter peaks; mean values for two independent experiments using pooled BM of Kat2a WT vs KO MLL-AF9 secondary leukemias. Mean enrichments: WT = 1.775, KO = 0.9609, 95% CI of difference 0.2640 to 1.364; 2-way ANOVA p<0.01 for genotype contribution.Figure 5—source data 1.D3E output analysis of cluster seven with annotation of Kat2a acetylation targets.