DNA methylation and complete transcriptional silencing of cancer genes persist after depletion of EZH2.
Recent work suggests a link between the polycomb group protein EZH2 and mediation of gene silencing in association with maintenance of DNA methylation. However, we show that whereas basally expressed target cancer genes with minimal DNA methylation have increased transcription during EZH2 knockdown, densely DNA hypermethylated and silenced genes retain their methylation and remain transcriptionally silent. These results suggest that EZH2 can modulate transcription of basally expressed genes but not silent genes that are densely DNA methylated.
McGarvey
Kelly M
KM
The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University, Baltimore, MD 21231, USA.
Greene
Eriko
E
Fahrner
Jill A
JA
Jenuwein
Thomas
T
Baylin
Stephen B
SB
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D000071221:Enhancer of Zeste Homolog 2 Protein; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism; D063151:Polycomb Repressive Complex 2; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D000070957:MutL Protein Homolog 1