Hatzi, K.Jiang, Y.Huang, C.Garrett-Bakelman, F.Gearhart, M.D.Giannopoulou, E.G.Zumbo, P.Kirouac, K.Bhaskara, S.Polo, J.M.Kormaksson, M.MacKerell, A.D.Xue, F.Mason, C.E.Hiebert, S.W.Prive, G.G.Cerchietti, L.Bardwell, V.J.Elemento, O.Melnick, A.2021-12-032021-12-032013Cell Reports, 2013; 4(3):578-5882211-12472211-1247https://hdl.handle.net/2440/133538The BCL6 transcriptional repressor is required for the development of germinal center (GC) B cells and diffuse large B cell lymphomas (DLBCLs). Although BCL6 can recruit multiple corepressors, its transcriptional repression mechanism of action in normal and malignant B cells is unknown. We find that in B cells, BCL6 mostly functions through two independent mechanisms that are collectively essential to GC formation and DLBCL, both mediated through its N-terminal BTB domain. These are (1) the formation of a unique ternary BCOR-SMRT complex at promoters, with each corepressor binding to symmetrical sites on BCL6 homodimers linked to specific epigenetic chromatin features, and (2) the "toggling" of active enhancers to a poised but not erased conformation through SMRT-dependent H3K27 deacetylation, which is mediated by HDAC3 and opposed by p300 histone acetyltransferase. Dynamic toggling of enhancers provides a basis for B cells to undergo rapid transcriptional and phenotypic changes in response to signaling or environmental cues.enThis is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative WorksLicense, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source arecreditedB-LymphocytesB-LymphocytesCell Line, TumorAnimalsHumansMiceDNA-Binding ProteinsSignal TransductionModels, MolecularProto-Oncogene Proteins c-bcl-6Lymphoma, Large B-Cell, DiffusePromoter Regions, GeneticHeterograftsJournal article10.1016/j.celrep.2013.06.0162021-12-03594200Polo, J.M. [0000-0002-2531-778X]