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.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Béguelin W,Teater M,Gearhart MD,Calvo Fernández MT,Goldstein RL,Cárdenas MG,Hatzi K,Rosen M,Shen H,Corcoran CM,Hamline MY,Gascoyne RD,Levine RL,Abdel-Wahab O,Licht JD,Shaknovich R,Elemento O,Bardwell VJ,Melnick AMdoi
10.1016/j.ccell.2016.07.006subject
Has Abstractpub_date
2016-08-08 00:00:00pages
197-213issue
2eissn
1535-6108issn
1878-3686pii
S1535-6108(16)30337-3journal_volume
30pub_type
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