Control of antigen presentation and interferon signaling by CREBBP-mediated antagonism of BCL6/HDAC3. (A) In CREBBP wild-type GCB cells, BCL6 regulates the DZ signature by recruiting the corepressor complexes, including SMRT–HDAC3, to repress its target genes. These genes are reactivated in the LZ by CREBBP. Inhibition of HDAC3 in CREBBP wild-type B cells leads to increased expression of these genes, including those with a role in antigen presentation and interferon signaling, due to the conserved role of the CREBBP/BCL6–HDAC3 regulatory axis in wild-type cells. (B) KAT domain mutation of CREBBP inhibit its catalytic activity and leads to a dominant-repressive effect by preventing the participation of redundant acetyltransferases in transactivation complexes. This leads to loss of antagonism to BCL6-mediated gene repression and reduced expression of antigen presentation and interferon signaling genes. These genes can be restored in CREBBP mutant cells by using an HDAC3-selective inhibitor.