| Literature DB >> 17560333 |
Raffaella Villa1, Diego Pasini, Arantxa Gutierrez, Lluis Morey, Manuela Occhionorelli, Emmanuelle Viré, Josep F Nomdedeu, Thomas Jenuwein, Pier Giuseppe Pelicci, Saverio Minucci, Francois Fuks, Kristian Helin, Luciano Di Croce.
Abstract
Epigenetic changes are common alterations in cancer cells. Here, we have investigated the role of Polycomb group proteins in the establishment and maintenance of the aberrant silencing of tumor suppressor genes during transformation induced by the leukemia-associated PML-RARalpha fusion protein. We show that in leukemic cells knockdown of SUZ12, a key component of Polycomb repressive complex 2 (PRC2), reverts not only histone modification but also induces DNA demethylation of PML-RARalpha target genes. This results in promoter reactivation and granulocytic differentiation. Importantly, the epigenetic alterations caused by PML-RARalpha can be reverted by retinoic acid treatment of primary blasts from leukemic patients. Our results demonstrate that the direct targeting of Polycomb group proteins by an oncogene plays a key role during carcinogenesis.Entities:
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Year: 2007 PMID： 17560333 DOI： 10.1016/j.ccr.2007.04.009
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743