| Literature DB >> 27505670 |
Wendy Béguelin1, Matt Teater2, Micah D Gearhart3, María Teresa Calvo Fernández1, Rebecca L Goldstein1, Mariano G Cárdenas1, Katerina Hatzi1, Monica Rosen1, Hao Shen1, Connie M Corcoran3, Michelle Y Hamline3, Randy D Gascoyne4, Ross L Levine5, Omar Abdel-Wahab5, Jonathan D Licht6, Rita Shaknovich1, Olivier Elemento7, Vivian J Bardwell8, Ari M Melnick9.
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.Entities:
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Year: 2016 PMID： 27505670 PMCID： PMC5000552 DOI： 10.1016/j.ccell.2016.07.006
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743