ABSTRACT
Abstract DNA methylation is an important type of epigenetic modification involved in gene regulation. Although strong DNA methylation at promoters is widely recognized to be associated with transcriptional repression, many aspects of DNA methylation remain not fully understood, including the quantitative relationships between DNA methylation and expression levels, and the individual roles of promoter and gene body methylation. Integrated analysis of whole-genome bisulfite sequencing and RNA sequencing data from human samples and cell lines find that while promoter methylation inversely correlates with gene expression as generally observed, the repressive effect is clear only on genes with a very high DNA methylation level. By means of statistical modeling, we find that DNA methylation is indicative of the expression class of a gene in general, but gene body methylation is a better indicator than promoter methylation. These findings are general in that a model constructed from a sample or cell line could accurately fit the unseen data from another. We will review the latest study on gene body methylation and discuss the possible mechanism how gene body methylation regulates gene expression. We also suggest that future studies on gene regulatory mechanisms and disease-associated differential methylation should pay more attention to DNA methylation at gene bodies and other non-promoter regions.
