Fig. 3.

CREBBP/EP300 mutations inhibited H3K27 acetylation and activated the NOTCH signaling pathway. a Structure prediction of the complex of CREBBP and EP300 mutations. b Protein expression of CREBBP and H3K27ac detected in vector, CREBBP^wt, CREBBP^R1392*, scramble, CREBBP^kd, protein expression of EP300 and H3K27ac in vector, EP300^wt, EP300^H1377R, scramble, EP300^kd of DB, SUDHL4, and LY10 cells by western blot. Tubulin and H3 were used as loading controls. The CREBBP/tubulin, EP300/tubulin, and H3K27ac/H3 ratio are shown. c Immunofluorescence assay of H3K27ac in CREBBP^R1392* and EP300^H1377R DB cells. d Immunohistochemical study of H3K27ac in tumor samples of diffuse large B-cell lymphoma (DLBCL) patients with and without CREBBP/EP300 mutations. e Pathway enrichment analysis in DLBCL patients with or without CREBBP/EP300 mutations according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. f Gene Set Enrichment Analysis (GSEA) enriched differentially expressed genes in NOTCH signaling pathway with or without CREBBP/EP300 mutations. Enrichment scores were listed with P value. NES normalized enrichment score, FDR false discovery rate. g Immunohistochemical study of NICD (intracellular portions of NOTCH1) in tumor samples of DLBCL patients with or without CREBBP/EP300 mutations