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Zinc finger protein Wiz links G9a/GLP histone methyltransferases to the co-repressor molecule CtBP.

G9a is a SET-domain mammalian histone methyltransferase responsible for mono- and dimethylation of lysine 9 in histone H3 (H3K9) at euchromatic regions. Recently we reported that G9a forms a stoichiometric heteromeric complex with another SET-domain-containing molecule, GLP/Eu-HMTase1. Although G9a and GLP can independently methylate H3K9 in vitro, G9a/GLP heteromeric formation seems to be essential for their function as a euchromatic H3K9 methyltransferase in vivo. To further elucidate how G9a/GLP-mediated histone methylation and transcriptional regulation are controlled, we purified and characterized G9a complexes from mouse embryonic stem cells. We identified a novel G9a/GLP-associating zinc finger molecule named Wiz that can interact with G9a and GLP independently but is more stable in the G9a/GLP heteromeric complexes. Interestingly, Wiz small inhibitory RNA knocks down not only Wiz but also G9a. GLP deficiency also decreases G9a levels, suggesting that the Wiz/G9a/GLP tri-complex may protect G9a from degradation and that Wiz plays a major role in G9a/GLP heterodimer formation. Furthermore, amino acid sequence analysis of Wiz predicted two potential CtBP binding sites, and indeed CtBP binding to Wiz and association of CtBP with the Wiz/G9a/GLP complex was observed. These data indicate that Wiz not only contributes to the stability of G9a but also links the G9a/GLP heteromeric complex to the CtBP co-repressor machinery.

Pubmed ID: 16702210

Authors

  • Ueda J
  • Tachibana M
  • Ikura T
  • Shinkai Y

Journal

The Journal of biological chemistry

Publication Data

July 21, 2006

Associated Grants

None

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Cells, Cultured
  • DNA Primers
  • Dimerization
  • Gene Silencing
  • Histone-Lysine N-Methyltransferase
  • Kruppel-Like Transcription Factors
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins
  • Protein Methyltransferases
  • Repressor Proteins
  • Stem Cells
  • Transcription Factors
  • Transcription, Genetic