Epigenetic regulation of survivin by Bmi1 is cell type specific during corticogenesis and in gliomas

Serena Acquati, Azzura Greco, Danilo Licastro, Heeta Bhagat, Dario Ceric, Zefferino Rossini, Joan Grieve, Maya Shaked-Rabi, Nick V. Henriquez, Sebastian Brandner, Elia Stupka, Silvia Marino

Research output: Contribution to journalArticle

Abstract

Polycomb group proteins are essential regulators of stem cell function during embryonic development and in adult tissue homeostasis. Bmi1, a key component of the Polycomb Repressive Complex 1, is highly expressed in undifferentiated neural stem cells (NSC) as well as in several human cancers including high-grade gliomas - highly aggressive brain tumors. Using a conditional gene activation approach in mice, we show that overexpression of Bmi1 induces repressive epigenetic regulation of the promoter of Survivin, a well-characterized antiapoptotic protein. This phenomenon is cell type-specific and it leads to apoptotic death of progenitor cells exclusively upon commitment toward a neuronal fate. Moreover, we show that this is triggered by increased oxidative stress-induced DNA damage. In contrast, undifferentiated NSC as well as glioma-initiating cells display an open chromatin configuration at the Survivin promoter and do not undergo apoptotic death. These findings raise the possibility that normal and neoplastic stem cells depend on the same mechanism for surviving the hyperproliferative state induced by increased Bmi1 expression.

Original languageEnglish
Pages (from-to)190-202
Number of pages13
JournalStem Cells
Volume31
Issue number1
DOIs
Publication statusPublished - Jan 2013

Keywords

  • Bmi1
  • DNA damage
  • Glioma
  • Neural stem cells
  • Oxidative stress
  • Survivin

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

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  • Cite this

    Acquati, S., Greco, A., Licastro, D., Bhagat, H., Ceric, D., Rossini, Z., Grieve, J., Shaked-Rabi, M., Henriquez, N. V., Brandner, S., Stupka, E., & Marino, S. (2013). Epigenetic regulation of survivin by Bmi1 is cell type specific during corticogenesis and in gliomas. Stem Cells, 31(1), 190-202. https://doi.org/10.1002/stem.1274