A hybrid mechanism of action for BCL6 in B cells defined by formation of functionally distinct complexes at enhancers and promoters

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dc.contributor.authorHatzi, K.
dc.contributor.authorJiang, Y.
dc.contributor.authorHuang, C.
dc.contributor.authorGarrett-Bakelman, F.
dc.contributor.authorGearhart, M.D.
dc.contributor.authorGiannopoulou, E.G.
dc.contributor.authorZumbo, P.
dc.contributor.authorKirouac, K.
dc.contributor.authorBhaskara, S.
dc.contributor.authorPolo, J.M.
dc.contributor.authorKormaksson, M.
dc.contributor.authorMacKerell, A.D.
dc.contributor.authorXue, F.
dc.contributor.authorMason, C.E.
dc.contributor.authorHiebert, S.W.
dc.contributor.authorPrive, G.G.
dc.contributor.authorCerchietti, L.
dc.contributor.authorBardwell, V.J.
dc.contributor.authorElemento, O.
dc.contributor.authorMelnick, A.
dc.date.issued2013
dc.description.abstractThe 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.
dc.description.statementofresponsibilityKaterina Hatzi, Yanwen Jiang, Chuanxin Huang, Francine Garrett-Bakelman, Micah D.Gearhart, Eugenia G.Giannopoulou
dc.identifier.citationCell Reports, 2013; 4(3):578-588
dc.identifier.doi10.1016/j.celrep.2013.06.016
dc.identifier.issn2211-1247
dc.identifier.issn2211-1247
dc.identifier.orcidPolo, J.M. [0000-0002-2531-778X]
dc.identifier.urihttps://hdl.handle.net/2440/133538
dc.language.isoen
dc.publisherCell Press
dc.relation.grantNHMRC
dc.rightsThis 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 arecredited
dc.source.urihttps://doi.org/10.1016/j.celrep.2013.06.016
dc.subjectB-Lymphocytes
dc.subject.meshB-Lymphocytes
dc.subject.meshCell Line, Tumor
dc.subject.meshAnimals
dc.subject.meshHumans
dc.subject.meshMice
dc.subject.meshDNA-Binding Proteins
dc.subject.meshSignal Transduction
dc.subject.meshModels, Molecular
dc.subject.meshProto-Oncogene Proteins c-bcl-6
dc.subject.meshLymphoma, Large B-Cell, Diffuse
dc.subject.meshPromoter Regions, Genetic
dc.subject.meshHeterografts
dc.titleA hybrid mechanism of action for BCL6 in B cells defined by formation of functionally distinct complexes at enhancers and promoters
dc.typeJournal article
pubs.publication-statusPublished

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