Roles of enhancer of zeste homolog 2: from skeletal muscle differentiation to rhabdomyosarcoma carcinogenesis.
Polycomb group proteins represent a global silencing system involved in embryonic development and stem-cell maintenance that regulates the transition from proliferation to differentiation during organogenesis. Two main complexes have been discovered: the polycomb repressive complex (PRC) 1 and 2, able to induce gene silencing by a synergistic mechanism or independently by each other. Enhancer of zeste homolog 2 (EZH2), the catalytic subunit of PRC2, represses gene transcription through the tri-methylation of histone H3 lysine 27. EZH2 deregulation is frequently associated with tumorigenesis, metastatic character, and poor prognosis in various cancer types. This review explores the role of EZH2 in normal development and in carcinogenesis. We reviewed the polycomb-mediated silencing mechanisms, the regulation of EZH2 activity and its recruitment to target genes. We also analyzed the role of EZH2 in normal muscle differentiation and in rhabdomyosarcoma, considering EZH2 blockade as a new strategy for developing specific therapies.
Department of Biomedical Sciences; Division of Biochemistry and National Institute of Biostructures and Biosystems; University of Sassari; Sassari, Italy.
Irene
I
Marchesi
Sbarro Institute for Cancer Research and Molecular Medicine; Center for Biotechnology; College of Science and Technology; Temple University; Philadelphia, PA USA; Human Pathology and Oncology Department; University of Siena; Siena, Italy.
Antonio
A
Giordano
Department of Biomedical Sciences; Division of Biochemistry and National Institute of Biostructures and Biosystems; University of Sassari; Sassari, Italy; Sbarro Institute for Cancer Research and Molecular Medicine; Center for Biotechnology; College of Science and Technology; Temple University; Philadelphia, PA USA.
Luigi
L
Bagella
D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D063150:Polycomb Repressive Complex 1 / Q000235:genetics / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D006657:Histones; D035683:MicroRNAs; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1
EZH2; cancer epigenetics; differentiation; myogenesis; polycomb group proteins; rhabdomyosarcoma,