Role of histone H3 lysine 27 methylation in Polycomb-group silencing.
Polycomb group (PcG) proteins play important roles in maintaining the silent state of HOX genes. Recent studies have implicated histone methylation in long-term gene silencing. However, a connection between PcG-mediated gene silencing and histone methylation has not been established. Here we report the purification and characterization of an EED-EZH2 complex, the human counterpart of the Drosophila ESC-E(Z) complex. We demonstrate that the complex specifically methylates nucleosomal histone H3 at lysine 27 (H3-K27). Using chromatin immunoprecipitation assays, we show that H3-K27 methylation colocalizes with, and is dependent on, E(Z) binding at an Ultrabithorax (Ubx) Polycomb response element (PRE), and that this methylation correlates with Ubx repression. Methylation on H3-K27 facilitates binding of Polycomb (PC), a component of the PRC1 complex, to histone H3 amino-terminal tail. Thus, these studies establish a link between histone methylation and PcG-mediated gene silencing.
D000818:Animals; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D020868:Gene Silencing; D005801:Genes, Homeobox; D006367:HeLa Cells; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism*; D018398:Homeodomain Proteins; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000302:isolation & purification / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D009707:Nucleosomes / Q000378:metabolism; D010449:Peptide Mapping; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D011233:Precipitin Tests; D011496:Protein Methyltransferases; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism; D034622:RNA Interference; D012097:Repressor Proteins / Q000302:isolation & purification / Q000378:metabolism; D020218:Response Elements; D013696:Temperature; D014157:Transcription Factors
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C491488:EED protein, human; D006657:Histones; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D009707:Nucleosomes; C116662:PRC1 protein, human; C066770:Pc protein, Drosophila; D011506:Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C066177:Ubx protein, Drosophila; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; C083329:E(z) protein, Drosophila; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; C543389:esc protein, Drosophila; D063150:Polycomb Repressive Complex 1; D008239:Lysine