DNA demethylation is superior to histone acetylation for reactivating cancer-associated genes in ovarian cancer cells

: To investigate the contributions of histone H3 lysine 9 acetylation and DNA methylation to p16, hMLH1 and MGMT silencing in ovarian cancer cells, we treated three ovarian cancer cell lines with Trichostatin A (TSA) and 5-aza-2'-deoxycytidine and examined the status of mRNA expression, DNA methylation and histone H3 lysine 9 acetylation at the promoter of p16, hMLH1 and MGMT. The results showed that the hypermethylated silenced tumor-related genes in the ovarian cancer cells were characterized by hypoacetylated histone H3 lysine 9. Treatment with TSA resulted in the increase of histone H3 lysine 9 acetylation at the hypermethylated promoter, but with little effects on gene expression. TSA did not contribute to DNA demethylation. 5-aza-2'-deoxycytidine treatment caused DNA demethylation, increased histone H3 lysine 9 acetylation at the hypermethylated promoter and resulted in reactivation of p16, hMLH1 and MGMT. Combined treatments synergistically increased histone H3 lysine 9 acetylation accompanied by the re-expression of the hypermethylated genes. To conclude, in ovarian cancer cells, DNA methylation and histone deacetylation act synergistically for the silencing of cancer-associated genes. DNA demethylation is superior to histone acetylation for reactivating cancer-associated genes.