CREBBP modulated programs in the GC. CREBBP positively modulates multiple biological programs in the GC, through acetylation of histone and nonhistone proteins (eg, BCL6 and p53) (left). Prominent roles include its ability to regulate antigen presentation/processing via control of CIITA expression, and to counteract the activity of BCL6 by a dual mechanism entailing acetylation-mediated inactivation of its protein and the deposition of H3K27Ac marks on the promoter/enhancer regions of its target genes, which facilitates an active chromatin conformation (bottom panel, with representative cobound genes). This switch may allow the rapid induction of genes that are required for post-GC differentiation in the LZ. CREBBP-modulated programs are disrupted in tumors carrying inactivating mutations of its gene (right). Ac, acetylated lysines.