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EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation

GSE45982 Mus musculus; Homo sapiens Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing 61 samples Submitted 2013/05/13 Platform GPL13112Platform GPL11154Platform GPL10999
Summary
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.
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Also filed as BioProject PRJNA198866 and SRA study SRP021509. Searching any of these in the dataset finder brings you back here.

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