EZH2 and BCL6 Cooperate to Assemble CBX8-BCOR Complex to Repress Bivalent Promoters, Mediate Germinal Center Formation and Lymphomagenesis.

Autor:	Béguelin W; Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA., Teater M; Division 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., Gearhart MD; Department 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., Calvo Fernández MT; Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA., Goldstein RL; Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA., Cárdenas MG; Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA., Hatzi K; Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA., Rosen M; Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA., Shen H; Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA., Corcoran CM; Department 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., Hamline MY; Department 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., Gascoyne RD; Departments of Pathology and Lymphoid Cancer Research, Centre for Lymphoid Cancer, British Columbia Cancer Agency, British Columbia Cancer Research Centre, Vancouver, BC, V5Z 1L3, Canada., Levine RL; Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA., Abdel-Wahab O; Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA., Licht JD; Division of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Shaknovich R; Division of Hematology/Oncology, Department of Medicine, Weill Cornell Medical College, Cornell University, 413 E 69(th) Street, New York, NY 10021, USA., Elemento O; Institute for Computational Biomedicine, Weill Cornell Medical College, Cornell University, New York, NY 10021, USA., Bardwell VJ; Department 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., Melnick AM; Division 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.
Jazyk:	angličtina
Zdroj:	Cancer cell [Cancer Cell] 2016 Aug 08; Vol. 30 (2), pp. 197-213.
DOI:	10.1016/j.ccell.2016.07.006
Abstrakt:	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. (Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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