The ablation of EZH2 uncovers its crucial role in rhabdomyosarcoma formation

Irene Marchesi, Francesco Paolo Fiorentino, Flavio Rizzolio, Antonio Giordano, Luigi Bagella

Research output: Contribution to journalArticlepeer-review

Abstract

Rhabdomyosarcoma (RMS) is a pediatric tumor that arises from muscle precursor cells. RMS cells express several markers of early myogenic diferentiation, but they fail to complete both diferentiation program and cell cycle arrest, resulting in uncontrolled proliferation and incomplete myogenesis. previous studies showed that eZH2, which is involved in both diferentiation 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 diferentiation program in RMS cells. In this study, we demonstrated that eZH2 directly binds muscle specifc genes in RD cells. Silencing of eZH2 promotes the recruitment of a multiprotein complex at muscle-specifc 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-specifc genes.

Original languageEnglish
Pages (from-to)3828-3836
Number of pages9
JournalCell Cycle
Volume11
Issue number20
DOIs
Publication statusPublished - Oct 15 2012

Keywords

  • EZH2
  • MyoD
  • Myogenesis
  • PRC complex
  • Rhabdomyosarcoma

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

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