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.
Pubmed ID: 15225548 RIS Download
Binding Sites | Cell Division | DNA-Binding Proteins | Enhancer of Zeste Homolog 2 Protein | 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 | Polycomb Repressive Complex 2 | Protein Methyltransferases | Proteins | Repressor Proteins | Silencer Elements, Transcriptional | Transcription Factors | Up-Regulation