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

Authors :
Villa, Raffaella
Pasini, Diego
Gutierrez, Arantxa
Morey, Lluis
Occhionorelli, Manuela
Viré, Emmanuelle
Nomdedeu, Josep F
Jenuwein, Thomas
Pelicci, Pier Giuseppe
Minucci, Saverio
Fuks, François
Helin, Kristian
Di Croce, Luciano
Villa, Raffaella
Pasini, Diego
Gutierrez, Arantxa
Morey, Lluis
Occhionorelli, Manuela
Viré, Emmanuelle
Nomdedeu, Josep F
Jenuwein, Thomas
Pelicci, Pier Giuseppe
Minucci, Saverio
Fuks, François
Helin, Kristian
Di Croce, Luciano
Source :
Cancer cell, 11 (6
Publication Year :
2007

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.<br />Journal Article<br />Research Support, Non-U.S. Gov't<br />SCOPUS: ar.j<br />info:eu-repo/semantics/published

Details

Database :
OAIster
Journal :
Cancer cell, 11 (6
Notes :
1 full-text file(s): application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.ocn764586168
Document Type :
Electronic Resource