Role of the polycomb repressive complex 2 in acute promyelocytic leukemia.

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.
Authors	Raffaella Villa, 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
Journal	Cancer cell (Cancer Cell) Vol. 11 Issue 6 Pg. 513-25 (Jun 2007) ISSN: 1535-6108 [Print] United States
PMID	17560333 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Carrier Proteins Histones Neoplasm Proteins Nuclear Proteins Oncogene Proteins, Fusion Polycomb-Group Proteins Repressor Proteins SUZ12 protein, human Transcription Factors promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein Tretinoin Polycomb Repressive Complex 2
Topics	Carrier Proteins (physiology) Cell Differentiation DNA Methylation Epigenesis, Genetic Gene Silencing Granulocytes (physiology) Histones Humans Leukemia, Promyelocytic, Acute (metabolism) Neoplasm Proteins Nuclear Proteins (physiology) Oncogene Proteins, Fusion (genetics, physiology) Polycomb Repressive Complex 2 Polycomb-Group Proteins Repressor Proteins (metabolism) Transcription Factors Tretinoin (pharmacology) Tumor Cells, Cultured

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