title: 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.affiliation: Centre de Regulacio Genomica, c/ Dr. Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Villa
authors.forename: Diego
authors.initials: D
authors.lastname: Pasini
authors.forename: Arantxa
authors.initials: A
authors.lastname: Gutierrez
authors.forename: Lluis
authors.initials: L
authors.lastname: Morey
authors.forename: Manuela
authors.initials: M
authors.lastname: Occhionorelli
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Viré
authors.forename: Josep F
authors.initials: JF
authors.lastname: Nomdedeu
authors.forename: Thomas
authors.initials: T
authors.lastname: Jenuwein
authors.forename: Pier Giuseppe
authors.initials: PG
authors.lastname: Pelicci
authors.forename: Saverio
authors.initials: S
authors.lastname: Minucci
authors.forename: Francois
authors.initials: F
authors.lastname: Fuks
authors.forename: Kristian
authors.initials: K
authors.lastname: Helin
authors.forename: Luciano
authors.initials: L
authors.lastname: Di Croce
mesh_terms: D002352:Carrier Proteins / Q000502:physiology*; D002454:Cell Differentiation; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006098:Granulocytes / Q000502:physiology; D006657:Histones; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D009363:Neoplasm Proteins; D009687:Nuclear Proteins / Q000502:physiology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology*; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000378:metabolism*; D014157:Transcription Factors; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D006657:Histones; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; C430461:SUZ12 protein, human; D014157:Transcription Factors; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; D014212:Tretinoin; D063151:Polycomb Repressive Complex 2