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

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.

• Authors: Ru Cao, Yi Zhang
• Journal: Molecular cell (Mol Cell) Vol. 15 Issue 1 Pg. 57-67 (Jul 02 2004) ISSN: 1097-2765 [Print] United States
• PMID: 15225548 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• AEBP2 protein, human
• DNA-Binding Proteins
• Histones
• Homeodomain Proteins
• Neoplasm Proteins
• Proteins
• Repressor Proteins
• SUZ12 protein, human
• 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

Topics

• 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, metabolism)
• Homeodomain Proteins (genetics)
• Humans
• Lysine (metabolism)
• Methylation
• Mutation (genetics)
• Neoplasm Proteins (genetics, metabolism)
• Polycomb Repressive Complex 2
• Protein Methyltransferases
• Proteins (genetics, metabolism)
• Repressor Proteins (genetics, metabolism)
• Silencer Elements, Transcriptional (genetics)
• Transcription Factors (genetics, metabolism)
• Up-Regulation (genetics)