SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex

Mol Cell. 2004 Jul 2;15(1):57-67. doi: 10.1016/j.molcel.2004.06.020.

Abstract

Recent studies have revealed the intrinsic histone methyltransferase (HMTase) activity of the EED-EZH2 complex and its role in Hox gene silencing, X inactivation, and cancer metastasis. In this study, we focus on the function of individual components. We found that the HMTase activity requires a minimum of three components-EZH2, EED, and SUZ12-while AEBP2 is required for optimal enzymatic activity. Using a stable SUZ12 knockdown cell line, we show SUZ12 knockdown results in cell growth defects, which correlate with genome-wide alteration on H3-K27 methylation as well as upregulation of a number of Hox genes. Chromatin immunoprecipitation (ChIP) assay identified a 500 bp region located 4 kb upstream of the HoxA9 transcription initiation site as a SUZ12 binding site, which responds to SUZ12 knockdown and might play an important role in regulating HoxA9 expression. Thus, our study establishes a critical role of SUZ12 in H3-lysine 27 methylation and Hox gene silencing.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding Sites / genetics
  • Cell Division / genetics
  • DNA-Binding Proteins
  • Enhancer of Zeste Homolog 2 Protein
  • Gene Expression Regulation, Developmental / genetics
  • Gene Silencing / physiology*
  • Gene Targeting
  • Genes, Homeobox / genetics*
  • HeLa Cells
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Histones / genetics
  • Histones / metabolism
  • Homeodomain Proteins / genetics
  • Humans
  • Lysine / metabolism
  • Methylation
  • Mutation / genetics
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Polycomb Repressive Complex 2
  • Protein Methyltransferases
  • Proteins / genetics
  • Proteins / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Silencer Elements, Transcriptional / genetics*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Up-Regulation / genetics

Substances

  • AEBP2 protein, human
  • DNA-Binding Proteins
  • Histones
  • Homeodomain Proteins
  • JJAZ1 protein, human
  • Neoplasm Proteins
  • Proteins
  • Repressor Proteins
  • Transcription Factors
  • homeobox protein HOXA9
  • Histone Methyltransferases
  • Protein Methyltransferases
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Histone-Lysine N-Methyltransferase
  • Polycomb Repressive Complex 2
  • Lysine