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.
Cao
Ru
R
Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Zhang
Yi
Y
D001665:Binding Sites / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D004268:DNA-Binding Proteins; D000071221:Enhancer of Zeste Homolog 2 Protein; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020868:Gene Silencing / Q000502:physiology*; D018390:Gene Targeting; D005801:Genes, Homeobox / Q000235:genetics*; D006367:HeLa Cells; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2; D011496:Protein Methyltransferases; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D037941:Silencer Elements, Transcriptional / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
C119809:AEBP2 protein, human; D004268:DNA-Binding Proteins; D006657:Histones; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D012097:Repressor Proteins; C430461:SUZ12 protein, human; D014157:Transcription Factors; C097899:homeobox protein HOXA9; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; D008239:Lysine