Methyl-CpG targeted transcriptional activation allows re-expression of tumor suppressor genes in human cancer cells

作者：Fukushige Shinichi^*; Kondo Emiko; Horii Akira

来源：Biochemical and Biophysical Research Communications, 2008, 377(2): 600-605.

DOI：10.1016/j.bbrc.2008.10.016

• MeTA
• Methyl-CpG binding domain
• CpG island
• Transcriptional repression
• Tumor suppressor genes
• MLH1
• Histone modifications
• NF kappa B transcriptional activation domain
• JMJD2D

DNA methylation and histone modifications are both major features of the epigenetic silencing seen at tumor suppressor genes (TSGs) in cancer. DNA methylation inhibitors, but not, in general, histone deacetylase, can reactivate TSGs. However, DNA methylation inhibitors frequently upregulate genes whose promoters remain unmethylated. Herein we demonstrated that the methyl-CpG targeted transcriptional activation (MeTA), which allows re-expression of TSGs without DNA demethylation, is widely seen in human cancer. We further analyzed MeTA and found that transcriptional coactivators are recruited at hypermethylated promoter regions of TSGs using the methyl-CpG binding domain (MBD). Reactivation of MLH1 by MeTA accompanied acetylation of histone H3 lysine 9/14 at the promoter region. Furthermore, all ten genes analyzed in three cell lines were reactivated by the effect of MeTA. Our present results lead to an efficient way to search for transcriptionally silenced genes with highly methylated CpG islands, particularly TSGs in cancer and developmentally important genes in embryonic stem cells.

• 出版日期2008-12-12