The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation
Open accessAbstract
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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Cites
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A bivalent chromatin structure marks key developmental genes in embryonic stem cells
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Role of Histone H3 Lysine 27 Methylation in Polycomb-Group Silencing
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Self-citationFrequent mutation of histone-modifying genes in non-Hodgkin lymphoma
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Genetic and epigenetic fine mapping of causal autoimmune disease variants
Farh, K. K.-H., Marson, A., Zhu, J., Kleinewietfeld, M., Housley, W. J., Beik, S., Shoresh, N., Whitton, H., Ryan, R. J. H., Shishkin, A. A., et al. (2015) · Nature · doi:10.1038/nature13835 · Cited by 1,956
Chapuy, B., Stewart, C., Dunford, A. J., Kim, J., Kamburov, A., Redd, R. A., Lawrence, M. S., Roemer, M. G. M., Li, A. J., Ziepert, M., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0016-8 · Cited by 1,941
Epigenetic plasticity and the hallmarks of cancer
Flavahan, W. A., Gaskell, E., & Bernstein, B. E. (2017) · Science · doi:10.1126/science.aal2380 · Cited by 1,340
Dynamics of B cells in germinal centres
De Silva, N. S., & Klein, U. (2015) · Nature Reviews Immunology · doi:10.1038/nri3804 · Cited by 1,084
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Metadata
- Authors
- Béguelin, W., Popovic, R., Teater, M., Jiang, Y., Bunting, K. L., Rosen, M., Shen, H., Yang, S. N., Wang, L., Ezponda, T., Martinez-Garcia, E., Zhang, H., Zheng, Y., Verma, S. K., McCabe, M. T., Ott, H. M., Van Aller, G. S., Kruger, R. G., Liu, Y., McHugh, C. F., Scott, D. W., Chung, Y. R., Kelleher, N., Shaknovich, R., Creasy, C. L., Gascoyne, R. D., Wong, K.-K., Cerchietti, L., Levine, R. L., Abdel-Wahab, O., Licht, J. D., Elemento, O., & Melnick, A. M.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 23
- Issue
- 5
- Pages
- 677-692
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2010711123
- Cited by
- 846
- References
- 6
- FWCI
- 46.03
- Type
- journal article
- Language
- en
- Open access
- bronze
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.