The consequences of CMG mutations on histone posttranslational modifications. (A) A depiction of the normal role of CMGs that are recurrently mutated in FL. KMT2C/D methylates H3K4, CREBBP and EP300 acetylate multiple residues including H3K18 and H3K27, and EZH2 catalyzes trimethylation of H3K27. (B) EZH2 Y641 mutation was predominantly associated with the gain of H3K27me3 at promoters already marked with H3K4me3, to form bivalent promoters. (C) KMT2D loss was associated with reduced H3K4 methylation at enhancer elements, including that for the TNFAIP3 gene. (D) CREBBP loss was associated with reduced H3K18Ac/H3K27Ac at enhancer elements, including those of major histocompatibility complex (MHC) class II genes.