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

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.
Mesh Terms:
Binding Sites, Cell Division, DNA-Binding Proteins, Gene Expression Regulation, Developmental, Gene Silencing, Gene Targeting, Genes, Homeobox, Hela Cells, Histone-Lysine N-Methyltransferase, Histones, Homeodomain Proteins, Humans, Lysine, Methylation, Mutation, Neoplasm Proteins, Protein Methyltransferases, Proteins, Repressor Proteins, Silencer Elements, Transcriptional, Transcription Factors, Up-Regulation
Mol. Cell
Date: Jul. 02, 2004
Download Curated Data For This Publication
92892
Switch View:
  • Interactions 9