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西亚试剂:Role of Nucleosomal Occupancy in the Epigenetic Silencing o

Role of Nucleosomal Occupancy in the Epigenetic Silencing of the MLH1 CpG Island

Joy C. Lin,1 Shinwu Jeong,1 Gangning Liang,1 Daiya Takai,1,2 Merhnaz Fatemi,1,3 Yvonne C. Tsai,1 Gerda Egger,1 Einav Nili Gal-Yam,1 and Peter A. Jones1,

1 Departments of Urology, Biochemistry, and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles, CA 90089, USA


Corresponding author
Peter A. Jones
Epigenetic silencing of tumor suppressor genes is generally thought to involve DNA cytosine methylation, covalent modifications of histones, and chromatin compaction. Here, we show that silencing of the three transcription start sites in the bidirectional MLH1 promoter CpG island in cancer cells involves distinct changes in nucleosomal occupancy. Three nucleosomes, almost completely absent from the start sites in normal cells, are present on the methylated and silenced promoter, suggesting that epigenetic silencing may be accomplished by the stable placement of nucleosomes into previously vacant positions. Activation of the promoter by demethylation with 5-aza-2′-deoxycytidine involves nucleosome eviction. Epigenetic silencing of tumor suppressor genes may involve heritable changes in nucleosome occupancy enabled by cytosine methylation.