The ablation of EZH2 uncovers its crucial role in rhabdomyosarcoma formation
Volume 11, Issue 20
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October 15, 2012
Pages 3828 - 3836http://dx.doi.org/10.4161/cc.22025
: EZH2, MyoD, PRC complex, myogenesis, rhabdomyosarcoma
Authors: Irene Marchesi, Francesco Paolo Fiorentino, Flavio Rizzolio, Antonio Giordano and Luigi Bagella View affiliations
Rhabdomyosarcoma (RMS) is a pediatric tumor that arises from muscle precursor cells. RMS cells express several markers of early myogenic differentiation, but they fail to complete both differentiation program and cell cycle arrest, resulting in uncontrolled proliferation and incomplete myogenesis. Previous studies showed that EZH2, which is involved in both differentiation and cancer progression, is overexpressed in RMS, but a functional binding between its expression and its functional role in tumor formation or progression has not yet been demonstrated. We hypothesized that EZH2 is a key regulator of muscular differentiation program in RMS cells.
In this study, we demonstrated that EZH2 directly binds muscle specific genes in RD cells. Silencing of EZH2 promotes the recruitment of a multiprotein complex at muscle-specific promoters, their transcriptional activation and protein expression. Moreover, we demonstrated that EZH2 is directly involved in transcriptional repression of MyoD, the main factor promoting myogenesis. EZH2 ablation induces MyoD activation the recovery of its binding on muscle-specific genes.
Received: March 13, 2012; Accepted: August 30, 2012; Published Online: September 14, 2012
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