| Literature DB >> 22237151 |
Panagiotis Ntziachristos1, Aristotelis Tsirigos, Pieter Van Vlierberghe, Jelena Nedjic, Thomas Trimarchi, Maria Sol Flaherty, Dolors Ferres-Marco, Vanina da Ros, Zuojian Tang, Jasmin Siegle, Patrik Asp, Michael Hadler, Isaura Rigo, Kim De Keersmaecker, Jay Patel, Tien Huynh, Filippo Utro, Sandrine Poglio, Jeremy B Samon, Elisabeth Paietta, Janis Racevskis, Jacob M Rowe, Raul Rabadan, Ross L Levine, Stuart Brown, Francoise Pflumio, Maria Dominguez, Adolfo Ferrando, Iannis Aifantis.
Abstract
T cell acute lymphoblastic leukemia (T-ALL) is an immature hematopoietic malignancy driven mainly by oncogenic activation of NOTCH1 signaling. In this study we report the presence of loss-of-function mutations and deletions of the EZH2 and SUZ12 genes, which encode crucial components of the Polycomb repressive complex 2 (PRC2), in 25% of T-ALLs. To further study the role of PRC2 in T-ALL, we used NOTCH1-dependent mouse models of the disease, as well as human T-ALL samples, and combined locus-specific and global analysis of NOTCH1-driven epigenetic changes. These studies demonstrated that activation of NOTCH1 specifically induces loss of the repressive mark Lys27 trimethylation of histone 3 (H3K27me3) by antagonizing the activity of PRC2. These studies suggest a tumor suppressor role for PRC2 in human leukemia and suggest a hitherto unrecognized dynamic interplay between oncogenic NOTCH1 and PRC2 function for the regulation of gene expression and cell transformation.Entities:
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Year: 2012 PMID： 22237151 PMCID： PMC3274628 DOI： 10.1038/nm.2651
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440