PLoS ONE (Jan 2012)

Histone demethylase Jumonji D3 (JMJD3) as a tumor suppressor by regulating p53 protein nuclear stabilization.

  • Chibawanye I Ene,
  • Lincoln Edwards,
  • Gregory Riddick,
  • Mehmet Baysan,
  • Kevin Woolard,
  • Svetlana Kotliarova,
  • Chen Lai,
  • Galina Belova,
  • Maggie Cam,
  • Jennifer Walling,
  • Ming Zhou,
  • Holly Stevenson,
  • Hong Sug Kim,
  • Keith Killian,
  • Timothy Veenstra,
  • Rolanda Bailey,
  • Hua Song,
  • Wei Zhang,
  • Howard A Fine

DOI
https://doi.org/10.1371/journal.pone.0051407
Journal volume & issue
Vol. 7, no. 12
p. e51407

Abstract

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Histone methylation regulates normal stem cell fate decisions through a coordinated interplay between histone methyltransferases and demethylases at lineage specific genes. Malignant transformation is associated with aberrant accumulation of repressive histone modifications, such as polycomb mediated histone 3 lysine 27 (H3K27me3) resulting in a histone methylation mediated block to differentiation. The relevance, however, of histone demethylases in cancer remains less clear. We report that JMJD3, a H3K27me3 demethylase, is induced during differentiation of glioblastoma stem cells (GSCs), where it promotes a differentiation-like phenotype via chromatin dependent (INK4A/ARF locus activation) and chromatin independent (nuclear p53 protein stabilization) mechanisms. Our findings indicate that deregulation of JMJD3 may contribute to gliomagenesis via inhibition of the p53 pathway resulting in a block to terminal differentiation.