EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation
By W. Béguelin, R. Popovic, Matt Teater, Yanwen Jiang, Karen L. Bunting, M. Rosen, Hao Shen, S. Yang, Ling Wang, Teresa Ezponda and 23 more. Cancer Cell, 2013
801 citations recorded by the source corpus.
The EZH2 histone methyltransferase is highly expressed in germinal center (GC) B-cells and targeted by somatic mutations in B-cell lymphomas. Here we find that EZH2 deletion or pharmacologic inhibition suppresses GC formation and functions in mice. EZH2 represses proliferation checkpoint genes and helps establish bivalent chromatin domains at key regulatory loci to transiently suppress GC B-cell differentiation. Somatic mutations reinforce these physiological effects through enhanced silencing of EZH2 targets in B-cells, and in human B-cell lymphomas. Conditional expression of mutant EZH2 in mice induces GC hyperplasia and accelerated lymphomagenesis in cooperation with BCL2. GCB-type DLBCLs are mostly addicted to EZH2, regardless of mutation status, but not the more differentiated ABC-type DLBCLs, thus clarifying the therapeutic scope of EZH2 targeting.
Subfields: Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/ea62cc7a978550cdbc69a73cbb18f3b35f92c51e
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In Immunology
In Molecular Biology
- Bradley E. Bernstein
- Gabriel D. Victora
- L. Mesin
- Jonatan Ersching
- William A. Flavahan
- Elizabeth Gaskell
- V. Schirrmacher
Citations in the corpus
- GERMINAL CENTER B CELL DYNAMICS (2016, positive): “Other recent developments have included the notions that epigenetic modifiers such as EZH2 and MOZ may influence the balance between PC and Bmem cell differentiation (Béguelin et al., 2013; Caganova et al., 2013; Good-Jacobson et al., 2014) and that mitochondrial function may provide instructive sig”
- Epigenetic plasticity and the hallmarks of cancer (2017, background): “For example, inactivating MLL2 and CBP/ p300mutations in lymphoma impede appropriate engagement of promoters or enhancers needed for differentiation, paralleling or potentially cooperatingwithEZH2gain-of-functionalleles (34,37,38).”