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
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Binding Sites / genetics
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Cell Division / genetics
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DNA-Binding Proteins
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Enhancer of Zeste Homolog 2 Protein
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Gene Expression Regulation, Developmental / genetics
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Gene Silencing / physiology*
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Gene Targeting
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Genes, Homeobox / genetics*
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HeLa Cells
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Histone Methyltransferases
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Histone-Lysine N-Methyltransferase / metabolism*
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Histones / genetics
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Histones / metabolism
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Homeodomain Proteins / genetics
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Humans
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Lysine / metabolism
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Methylation
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Mutation / genetics
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Polycomb Repressive Complex 2
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Protein Methyltransferases
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Proteins / genetics
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Proteins / metabolism*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Silencer Elements, Transcriptional / genetics*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Up-Regulation / genetics
Substances
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AEBP2 protein, human
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DNA-Binding Proteins
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Histones
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Homeodomain Proteins
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Neoplasm Proteins
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Proteins
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Repressor Proteins
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SUZ12 protein, human
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Transcription Factors
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homeobox protein HOXA9
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Histone Methyltransferases
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Protein Methyltransferases
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EZH2 protein, human
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Enhancer of Zeste Homolog 2 Protein
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Histone-Lysine N-Methyltransferase
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Polycomb Repressive Complex 2
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Lysine