| Literature DB >> 24183680 |
Sebastian Bender1, Yujie Tang, Anders M Lindroth, Volker Hovestadt, David T W Jones, Marcel Kool, Marc Zapatka, Paul A Northcott, Dominik Sturm, Wei Wang, Bernhard Radlwimmer, Jonas W Højfeldt, Nathalène Truffaux, David Castel, Simone Schubert, Marina Ryzhova, Huriye Seker-Cin, Jan Gronych, Pascal David Johann, Sebastian Stark, Jochen Meyer, Till Milde, Martin Schuhmann, Martin Ebinger, Camelia-Maria Monoranu, Anitha Ponnuswami, Spenser Chen, Chris Jones, Olaf Witt, V Peter Collins, Andreas von Deimling, Nada Jabado, Stephanie Puget, Jacques Grill, Kristian Helin, Andrey Korshunov, Peter Lichter, Michelle Monje, Christoph Plass, Yoon-Jae Cho, Stefan M Pfister.
Abstract
Two recurrent mutations, K27M and G34R/V, within histone variant H3.3 were recently identified in ∼50% of pHGGs. Both mutations define clinically and biologically distinct subgroups of pHGGs. Here, we provide further insight about the dominant-negative effect of K27M mutant H3.3, leading to a global reduction of the repressive histone mark H3K27me3. We demonstrate that this is caused by aberrant recruitment of the PRC2 complex to K27M mutant H3.3 and enzymatic inhibition of the H3K27me3-establishing methyltransferase EZH2. By performing chromatin immunoprecipitation followed by next-generation sequencing and whole-genome bisulfite sequencing in primary pHGGs, we show that reduced H3K27me3 levels and DNA hypomethylation act in concert to activate gene expression in K27M mutant pHGGs.Entities:
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Year: 2013 PMID： 24183680 DOI： 10.1016/j.ccr.2013.10.006
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743