Abstract
DNA methylation has crucial roles in gene regulation of mammalian cells. DNA methyltransferases (DNMTs) typically add methyl groups to the cytosine in a CpG dinucleotide context [1]. Approximately 70% of the total number of CpG sites in the mammalian genome are methylated, and intragenic regions account for approximately 40% of methylated CpG sites [2]. However, sites in CpG islands (CGIs), which have an elevated G+C composition, frequently lack DNA methylation and are associated with the promoters of 60% of annotated genes, including promoters of all the housekeeping genes [1]. DNA methylation in promoters generally has a stable gene-silencing effect; however, methylation in intragenic regions is not always associated with gene repression. Currently, the roles of intragenic CGIs are not well defined, but several interesting clues regarding its regulatory functions in gene expression have begun to emerge. For example, intragenic DNA methylation was shown to influence transcriptional elongation and alternative splicing, and abnormal DNA methylation has frequently been associated with cancer progression. To emphasize the importance of intragenic DNA methylation in gene expression, this commentary will discuss its regulatory mechanisms based on recent studies.
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