Fig. 5

EP300/CBP-regulated genes are affected by AD-associated epigenomic dysregulation. A–D GSEA plots depicting the placement of genes significantly downregulated by EP300 KD in APPDup neurons (A), genes significantly downregulated by CBP KD in APPDup neurons (B), genes significantly downregulated by EP300 KD in NDC neurons (C), and genes significantly downregulated by CBP KD in NDC neurons (D), identified in this study, within the RNA-seq transcriptome of human whole brain, ranked from highest expressed in AD patient brains to highest expressed in non-demented age-matched (“Old”) brains from Nativio et al. 2018. E Significant overlap was observed between APPDup EP300/CBP KDDownregulated genes and Old-associated genes (N = 120, Jaccard = 120/3718, p = 2.61e-08), but not between and APPDup EP300/CBP KD-downregulated genes and AD-associated genes (N = 64, Jaccard = 64/3718, p = 0.613). Hypergeometric statistical testing was performed using the SuperExactTest R package. F EP300- and CBP-regulated genes in APPDup neurons are significantly associated with either AD-specific or Old-specific H3K27ac enrichment in human postmortem tissue, when contrasted with a control group of HAT-insensitive background genes that have nearby H3K27ac enrichment in the same brains. Statistical significance calculated using permutation test