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

Overview

MeSH Major

  • Enhancer of Zeste Homolog 2 Protein
  • Germinal Center
  • Lymphoma, Large B-Cell, Diffuse
  • Polycomb Repressive Complex 1
  • Proto-Oncogene Proteins c-bcl-6
  • Repressor Proteins

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.

publication date

  • August 8, 2016

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5000552

Digital Object Identifier (DOI)

  • 10.1016/j.ccell.2016.07.006

PubMed ID

  • 27505670

Additional Document Info

start page

  • 197

end page

  • 213

volume

  • 30

number

  • 2