Background: DNA methylation is an epigenetic modification that plays an important
role in regulating gene expression. There is evidence that the hypermethylation of promoter regions
always causes gene silencing. However, how the methylation patterns of other regions in the
genome, such as gene body and 3’UTR, affect gene expression is unknown.
Objective: The study aimed to fully explore the relationship between DNA methylation and expression
throughout the genome-wide analysis which is important in understanding the function of
DNA methylation essentially.
Method: In this paper, we develop a heuristic framework to analyze the relationship between the
methylated change in different regions and that of the corresponding gene expression based on differential
Results: To understande the methylated function of different genomic regions, a gene is divided
into seven functional regions. By applying the method in five cancer datasets from the Synapse database,
it was found that methylated regions with a significant difference between cases and controls
were almost uniformly distributed in the seven regions of the genome. Also, the effect of
DNA methylation in different regions on gene expression was different. For example, there was a
higher percentage of positive relationships in 1stExon, gene body and 3’UTR than in TSS1500 and
TSS200. The functional analysis of genes with a significant positive and negative correlation between
DNA methylation and gene expression demonstrated the epigenetic mechanism of cancerassociated
Conclusion: Differential based analysis helps us to recognize the change in DNA methylation and
how this change affects the change in gene expression. It provides a basis for further integrating
gene expression and DNA methylation data to identify disease-associated biomarkers.