The ZNF217 oncogene is a candidate organizer of repressive histone modifiers

Epigenetics. 2009 Feb 16;4(2):100-6. doi: 10.4161/epi.4.2.7953. Epub 2009 Feb 23.

Abstract

The zinc finger protein 217 (ZNF217) is an important oncogene based on the high frequency of amplification and overexpression in many cancer types, but its molecular mode of gene regulation is poorly understood. We purified a complex of nuclear ZNF217-binding proteins by affinity chromatography and identified its components by mass spectrometry as Jarid1b/Plu-1, G9a, LSD1, CoREST and CtBP1. Individual binding of these with ZNF217 was confirmed by co-immunoprecipiation (IP). Known activities of these proteins suggested a role of the ZNF217 complex in histone modification. Using in vitro assays the following activities were demonstrated: Histone H3 lysine 4 trimethyl (H3K4me3) demethylase activity, which co-fractionated with Jarid1b/Plu-1 in anion-exchange chromatography; H3K9 methylation, the known principal activity of G9a; and H3K27 methylation. The latter suggested EZH2 as another ZNF217 binding candidate, which could be confirmed by co-IP. Taken together, these findings suggest that ZNF217 assembles a distinct set of histone modifying proteins at target DNA sites that act synergistically in transcriptional repression.

Publication types

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

MeSH terms

  • Cell Line, Tumor
  • DNA-Binding Proteins / metabolism
  • Down-Regulation / genetics
  • Enhancer of Zeste Homolog 2 Protein
  • Gene Expression Regulation*
  • Histones / metabolism*
  • Humans
  • Jumonji Domain-Containing Histone Demethylases
  • Neoplasm Proteins
  • Nuclear Proteins / metabolism
  • Oncogenes
  • Oxidoreductases, N-Demethylating / metabolism
  • Polycomb Repressive Complex 2
  • Protein Binding
  • Protein Processing, Post-Translational
  • Repressor Proteins / metabolism
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Trans-Activators / physiology
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • Histones
  • Neoplasm Proteins
  • Nuclear Proteins
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors
  • ZNF217 protein, human
  • Jumonji Domain-Containing Histone Demethylases
  • KDM5B protein, human
  • Oxidoreductases, N-Demethylating
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2