The Essential Role of Histone H3 Lys9 Di-Methylation and MeCP2 Binding in MGMT Silencing with Poor DNA Methylation of the Promoter CpG Island

摘要: Silencing of the O (6)-methylguanine-DNA methyltransferase (MGMT) gene, a key to DNA repair, is involved in carcinogenesis. Recent studies have focused on hypermethylation promoter CpG island. However, cases showing silencing with hypomethylation certainly exist, and mechanism not elucidated. To clarify this mechanism, we examined dynamics methylation, histone acetylation, binding methyl-CpG proteins at MGMT region using four negative cell lines various extents methylation. Histone H3K9 di-methylation (H3me2K9), tri-methylation, MeCP2 were commonly seen all regardless methylation status. 5Aza-dC, but TSA, restored gene expression, accompanied by decrease H3me2K9 binding. In SaOS2 cells most hypomethylated island, 5Aza-dC decreased no effect or acetylation. restricted around indicating that epigenetic modification island critical. We conclude are common more essential for than deacetylation. The leading silent heterochromatin may be same different types cancer irrespective extent