TitleEZH2 and BCL6 Cooperate to Assemble CBX8-BCOR Complex to Repress Bivalent Promoters, Mediate Germinal Center Formation and Lymphomagenesis.
Publication TypeJournal Article
Year of Publication2016
AuthorsBéguelin, Wendy, Teater Matt, Gearhart Micah D., Fernández María Teresa Cal, Goldstein Rebecca L., Cardenas Mariano G., Hatzi Katerina, Rosen Monica, Shen Hao, Corcoran Connie M., Hamline Michelle Y., Gascoyne Randy D., Levine Ross L., Abdel-Wahab Omar, Licht Jonathan D., Shaknovich Rita, Elemento Olivier, Bardwell Vivian J., and Melnick Ari M.
JournalCancer Cell
Date Published2016 Aug 08
KeywordsAnimals, Enhancer of Zeste Homolog 2 Protein, Germinal Center, Humans, Lymphoma, Large B-Cell, Diffuse, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mitochondrial Membrane Transport Proteins, Polycomb Repressive Complex 1, Polycomb-Group Proteins, Promoter Regions, Genetic, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-6, Repressor Proteins, Transcription, Genetic

<p>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.</p>

Alternate JournalCancer Cell
PubMed ID27505670
PubMed Central IDPMC5000552
Grant ListR01 CA187109 / CA / NCI NIH HHS / United States
R01 CA194547 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
F30 HL093996 / HL / NHLBI NIH HHS / United States
T32 GM008244 / GM / NIGMS NIH HHS / United States
R01 CA104348 / CA / NCI NIH HHS / United States
R01 CA071540 / CA / NCI NIH HHS / United States