Dynamic loading of CREBBP and EP300 during the CB-to-CC cell state transition. (A-B) Heat maps (A) and density plots (B) of regions with significantly (FDR <0.05) different loading of CREBBP (left) and EP300 (right) between CBs and CCs. (C) Number of peaks with dynamic loading (green) or unloading (blue) of CREBBP or EP300 in the CB-to-CC transition. (D) Overlap of regions with differential loading of CREBBP or EP300 in CBs and CCs. (E) Quantification of the change in CREBBP loading between KAT-PM (R1446C, Y1482N, Y1503C) and WT cells over regions with dynamic loading of CREBBP or EP300 in the CB-to-CC transition (regions from panel C). (F) Heat map of CREBBP loading in isogenic WT and CREBBP KAT-PM (average of R1446C, Y1482N, Y1503C) cells over regions with significantly increased CREBBP loading in CC compared with CB. ∗∗∗P < 2.2 × 10^–16. (G) Hypergeometric gene set enrichment analysis (hGSEA) of genes associated with peaks with or without differential loading of CREBBP or EP300 in the CB-to-CC transition (corresponding to panel C) or with significant loss of CREBBP loading in KAT-PM cells compared with isogenic WT controls. (H) TF motif enrichment analysis (HOMER) of peaks with or without differential loading of CREBBP or EP300 in the CB-to-CC transition (corresponding to panel C). (I) Tracks showing the CD74 locus as a representative example of regions with significant (FDR < 0.05; highlighted in yellow) gain in CREBBP loading in the CB-to-CC transition and loss of CREBBP loading in KAT-PM cells compared with isogenic WT controls in both CRISPR engineered cell lines (RL and HT) and primary FL tumor cells. Tracks represent overlays of biological replicates.