Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as a potential therapeutic target

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dc.contributor.author Singh, Umashankar
dc.date.accessioned 2016-04-16T16:41:43Z
dc.date.available 2016-04-16T16:41:43Z
dc.date.issued 2016-01
dc.identifier.citation Singh, Umashankar et al., “Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as a potential therapeutic target”, Oncotarget, DOI: 10.18632/oncotarget.6843, vol. 7, pp. 6, pp. 6809–6823,7, Jan. 2016. en_US
dc.identifier.issn 1949-2553
dc.identifier.uri http://dx.doi.org/10.18632/oncotarget.6843
dc.identifier.uri https://repository.iitgn.ac.in/handle/123456789/2204
dc.description.abstract Multiple myeloma (MM) is a malignancy of the antibody-producing plasma cells. MM is a highly heterogeneous disease, which has hampered the identification of a common underlying mechanism for disease establishment as well as the development of targeted therapy. Here we present the first genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in MM patient samples, defining a common set of active H3K4me3-enriched genes and silent genes marked by H3K27me3 (H3K27me3 alone or bivalent) unique to primary MM cells, when compared to normal bone marrow plasma cells. Using this epigenome profile, we found increased silencing of H3K27me3 targets in MM patients at advanced stages of the disease, and the expression pattern of H3K27me3-marked genes correlated with poor patient survival. We also demonstrated that pharmacological inhibition of EZH2 had anti-myeloma effects in both MM cell lines and CD138+ MM patient cells. In addition, EZH2 inhibition decreased the global H3K27 methylation and induced apoptosis. Taken together, these data suggest an important role for the Polycomb repressive complex 2 (PRC2) in MM, and highlights the PRC2 component EZH2 as a potential therapeutic target in MM. en_US
dc.description.statementofresponsibility by Umashankar Singh et al.
dc.format.extent Vol. 7, pp. 6, pp. 6809–6823
dc.language.iso en_US en_US
dc.publisher Impact Journals en_US
dc.subject Multiple myeloma en_US
dc.subject Polycomb en_US
dc.subject EZH2 en_US
dc.subject H3K27me3 en_US
dc.subject UNC1999 en_US
dc.title Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as a potential therapeutic target en_US
dc.type Article en_US
dc.relation.journal Oncotarget


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