DNA methylation and complete transcriptional silencing of cancer genes persist after depletion of EZH2

Cancer Res. 2007 Jun 1;67(11):5097-102. doi: 10.1158/0008-5472.CAN-06-2029.

Abstract

Recent work suggests a link between the polycomb group protein EZH2 and mediation of gene silencing in association with maintenance of DNA methylation. However, we show that whereas basally expressed target cancer genes with minimal DNA methylation have increased transcription during EZH2 knockdown, densely DNA hypermethylated and silenced genes retain their methylation and remain transcriptionally silent. These results suggest that EZH2 can modulate transcription of basally expressed genes but not silent genes that are densely DNA methylated.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis
  • Adaptor Proteins, Signal Transducing / genetics
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / metabolism
  • Cell Line, Tumor
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / metabolism
  • DNA Methylation*
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics*
  • Enhancer of Zeste Homolog 2 Protein
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing*
  • Genes, Tumor Suppressor
  • Humans
  • MutL Protein Homolog 1
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism
  • Polycomb Repressive Complex 2
  • RNA, Small Interfering
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics*
  • Transcription, Genetic
  • Transfection

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • MLH1 protein, human
  • Nuclear Proteins
  • RNA, Small Interfering
  • Transcription Factors
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2
  • MutL Protein Homolog 1