Jump to Main Contents
研究所ロゴ

Home > Organization > Divisions and Independent Research Units > Group for Development of Molecular diagnostics and Individualized Therapy > Division of Epigenomics > Research Projects > Genes susceptible to induction of aberrant DNA methylation

Genes susceptible to induction of aberrant DNA methylation

Both aberrant DNA methylation and mutations can inactivate tumor-suppressor genes. We revealed that, in contrast to mutations, aberrant DNA methylation is induced at specific genes. Specific genes were methylated in gastric mucosae of individuals infected by Helicobacter pylori (Nakajima et al., 2009 ), and DNA methylation levels of specific genes were increased in esophageal mucosae of individuals with prolonged smoking history (Oka et al., 2009 ).

Regarding the mechanisms why specific genes are methylated, we previously revealed that genes with no or low expression are susceptible to induction of aberrant DNA methylation. For example, most genes methylated in pancreatic cancers (Hagihara et al., 2004 ) or melanomas (Furuta et al., 2006 ) had no or low expression in their normal counterpart cells. In addition, using DNA methylation microarray analysis, we revealed that most genes methylated in prostate cancers and breast cancers had no or low expression in normal prostate and mammary glands, respectively (Takeshima et al., 2009 ).

Furthermore, we intended to clarify why some genes with no or low expression were still resistant to induction of aberrant DNA methylation. To this end, we analyzed active and inactive histone modifications and RNA polymerase II (Pol II) binding status of these genes, and revealed that active histone modifications and Pol II are highly accumulated at promoter regions of resistant genes (Takeshima et al., 2009 ). In other words, genes that are standing by for future expression are resistant to induction of aberrant DNA methylation even if they are not expressed now (Fig. ).

Our finding can be interpreted as "genes used or ready to be used do not rust (become methylated) easily". Well-balanced meals and occasional change of life styles lead to expression of various genes, and there is a possibility that the use of various genes is effective in preventing genes from rusting.

induction of aberrant DNA methylation

Fig. Instructive mechanism for induction of aberrant DNA methylation.
Genes with high expression level are resistant to induction of aberrant DNA methylation. In addition, genes that are standing by for future expression are also resistant to induction of aberrant DNA methylation. In contrast, genes that are not ready for future expression are susceptible to induction of aberrant DNA methylation.