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

被引：208

作者：

Beguelin, Wendy ^{[1
]}

Teater, Matt ^{[1
,2
]}

Gearhart, Micah D. ^{[3
]}

Fernandez, Maria Teresa Calvo ^{[1
]}

Goldstein, Rebecca L. ^{[1
]}

Cardenas, Mariano G. ^{[1
]}

Hatzi, Katerina ^{[1
]}

Rosen, Monica ^{[1
]}

Shen, Hao ^{[1
]}

Corcoran, Connie M. ^{[3
]}

Hamline, Michelle Y. ^{[3
,8
]}

Gascoyne, Randy D. ^{[4
,5
]}

Levine, Ross L. ^{[6
]}

Abdel-Wahab, Omar ^{[6
]}

Licht, Jonathan D. ^{[7
]}

Shaknovich, Rita ^{[1
]}

Elemento, Olivier ^{[2
]}

Bardwell, Vivian J. ^{[3
]}

Melnick, Ari M. ^{[1
]}

机构：

[1] Cornell Univ, Div Hematol Oncol, Dept Med, Weill Cornell Med Coll, 413 E 69th St, New York, NY 10021 USA

[2] Cornell Univ, Inst Computat Biomed, Weill Cornell Med Coll, New York, NY 10021 USA

[3] Univ Minnesota, Masonic Canc Ctr, Ctr Dev Biol, Dept Genet Cell Biol & Dev, 6-160 Church St SE, Minneapolis, MN 55455 USA

[4] British Columbia Canc Res Ctr, British Columbia Canc Agcy, Ctr Lymphoid Canc, Dept Pathol, Vancouver, BC V5Z 1L3, Canada

[5] British Columbia Canc Res Ctr, British Columbia Canc Agcy, Ctr Lymphoid Canc, Dept Lymphoid Canc Res, Vancouver, BC V5Z 1L3, Canada

[6] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

[7] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Div Hematol Oncol, Chicago, IL 60611 USA

[8] Univ Calif Davis, Med Ctr, Dept Pediat, Sacramento, CA 95817 USA

来源：

CANCER CELL | 2016年 / 30卷 / 02期

关键词：

HISTONE H3 METHYLATION; POLYCOMB GROUP PROTEIN; B-CELL LYMPHOMAS; BCOR; EXPRESSION; MUTATIONS; PATHOGENESIS; RECRUITMENT; INHIBITOR; REVEALS;

D O I：

10.1016/j.ccell.2016.07.006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：197 / 213

页数：17

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