ArticleCancer cell2016
EZH2 and BCL6 Cooperate to Assemble CBX8-BCOR Complex to Repress Bivalent Promoters, Mediate Germinal Center Formation and Lymphomagenesis.
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Article in Cancer cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers.
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161citing papers in PubMed
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161 citing papers in PubMed, 247 citations in OpenAlex.
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- BCOR Mutations Deregulate Cell Cycle and Hypoxic Adaptation Pathways in Retinoblastoma.Molecular cancer research : MCR · 2026Article
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- T follicular helper cells transiently unlock a plasticity state in germinal centre B cells during the humoral immune response.Nature cell biology · 2026Article
- Mouse models of B cell lymphomas on the basis of genetic features.Frontiers in immunology · 2026Review
- Novel Small Molecule DZ-865B Effectively Degrades BCL6, Promotes Apoptosis and Reduces Proliferation of Diffuse Large B-Cell Lymphoma Cells.Oncology research · 2026Article
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- Overcoming CAR-T bottlenecks in high-risk DLBCL: a molecular subtyping enhancement strategy.Cancer cell international · 2025Review
- In vivo CRISPR screening reveals cooperation of KMT2D and TP53 deficiencies in B-cell lymphomagenesis.Blood advances · 2025Article
101 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 5 institutions in 2 countries.
Wendy BéguelinDivision of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA.
Matt TeaterDivision of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA; Institute for Computational Biomedicine, Weill Cornell Medical College, Cornell University, New York, NY 10021, USA.
Micah D GearhartDepartment of Genetics, Cell Biology, and Development, Developmental Biology Center, Masonic Cancer Center, University of Minnesota, 6-160 Church Street SE, University of Minnesota, Minneapolis, MN 55455, USA.
María Teresa Calvo FernándezDivision of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA.
Rebecca L GoldsteinDivision of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA.
Mariano G CárdenasDivision of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA.
Katerina HatziDivision of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA.
Monica RosenDivision of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA.
Hao ShenDivision of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA.
Connie M CorcoranDepartment of Genetics, Cell Biology, and Development, Developmental Biology Center, Masonic Cancer Center, University of Minnesota, 6-160 Church Street SE, University of Minnesota, Minneapolis, MN 55455, USA.
Michelle Y HamlineDepartment of Genetics, Cell Biology, and Development, Developmental Biology Center, Masonic Cancer Center, University of Minnesota, 6-160 Church Street SE, University of Minnesota, Minneapolis, MN 55455, USA.
Randy D GascoyneDepartments of Pathology and Lymphoid Cancer Research, Centre for Lymphoid Cancer, British Columbia Cancer Agency, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada.
Ross L LevineHuman Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Omar Abdel-WahabHuman Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Jonathan D LichtDivision of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Rita ShaknovichDivision of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA.
Olivier ElementoInstitute for Computational Biomedicine, Weill Cornell Medical College, Cornell University, New York, NY 10021, USA.
Vivian J BardwellDepartment of Genetics, Cell Biology, and Development, Developmental Biology Center, Masonic Cancer Center, University of Minnesota, 6-160 Church Street SE, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: bardw001@umn.edu.
Ari M MelnickDivision of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA. Electronic address: amm2014@med.cornell.edu.
Cornell University · USUniversity of Minnesota · USMemorial Sloan Kettering Cancer Center · USBC Cancer Agency · CANorthwestern University · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MMEDICAL SCIENTIST TRAINING PROGRAMT32GM008244 · NIGMS · UNIVERSITY OF MINNESOTA TWIN CITIES · PI SHIMIZU, YOJI · 1988 to 2024
$13.6MMolecular Basis of Action of the Putative Oncogene BCL6R01CA071540 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI BARDWELL, VIVIAN J · 2002 to 2012
$3.0MThe identification and validation of mechanisms and biomarkers for relapse in diffuse large B-cell lymphoma (Administrative Supplement)R01CA194547 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI ELEMENTO, OLIVIER, TAM, WAYNE · 2015 to 2019
$2.6MTranscriptional silencing by the BCL6 oncoproteinR01CA104348 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI MELNICK, ARI M. · 2004 to 2014
$2.6MTargeting EZH2 in Germinal Center Derived B-Cell LymphomaR01CA187109 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI MELNICK, ARI M. · 2014 to 2017
$1.8MBCOR in cardiovascular developmentF30HL093996 · NHLBI · UNIVERSITY OF MINNESOTA · PI HAMLINE, MICHELLE YVONNE · 2008 to 2012
$107kNCI NIH HHS P30 CA008748NCI NIH HHS R01 CA071540NCI NIH HHS R01 CA104348NCI NIH HHS R01 CA187109NCI NIH HHS R01 CA194547NHLBI NIH HHS F30 HL093996NIGMS NIH HHS T32 GM008244
Abstract
The EZH2 histone methyltransferase mediates the humoral immune response and drives lymphomagenesis through formation of bivalent chromatin domains at critical germinal center (GC) B cell promoters. Herein we show that the actions of EZH2 in driving GC formation and lymphoma precursor lesions require site-specific binding by the BCL6 transcriptional repressor and the presence of a non-canonical PRC1-BCOR-CBX8 complex. The chromodomain protein CBX8 is induced in GC B cells, binds to H3K27me3 at bivalent promoters, and is required for stable association of the complex and the resulting histone modifications. Moreover, oncogenic BCL6 and EZH2 cooperate to accelerate diffuse large B cell lymphoma (DLBCL) development and combinatorial targeting of these repressors results in enhanced anti-lymphoma activity in DLBCLs.
Indexed as
AnimalsEnhancer of Zeste Homolog 2 ProteinGerminal CenterHumansLymphoma, Large B-Cell, DiffuseMiceMice, Inbred C57BLMice, TransgenicMitochondrial Membrane Transport ProteinsPolycomb-Group ProteinsPolycomb Repressive Complex 1Promoter Regions, GeneticProto-Oncogene ProteinsProto-Oncogene Proteins c-bcl-6Repressor ProteinsTranscription, GeneticBCL6 protein, humanBcl6 protein, mouseBCOR protein, humanBcor protein, mouseCBX8 protein, humanCbx8 protein, mouseEnhancer of Zeste Homolog 2 ProteinEZH2 protein, humanEzh2 protein, mouseMitochondrial Membrane Transport ProteinsPolycomb-Group ProteinsPolycomb Repressive Complex 1Proto-Oncogene ProteinsProto-Oncogene Proteins c-bcl-6Repressor Proteins
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