Investigating the role of CpG island DNA methylation at 3'UTRs in cancer

Abstract

DNA methylation is one of the most important epigenetic processes that regulates gene expression. While the human genome is predominately methylated, CpG-rich regions known as CpG islands (CGIs) are unmethylated and are sites of transcriptional control. While the importance of CGI and DNA methylation at gene promoters is well understood, the significance of CGIs at 3 untranslated regions (3UTRs) remains largely unexplored. In this study, we characterised CGIs located within 3UTRs and investigated their role in gene regulation. Here, we show that around 3% of CGIs (909 CGIs) are exclusively located at 3UTR and are not associated with any nearby promoters. Importantly, 3UTR CGIs are highly conserved, with a conservation score even higher than promoter CGI implying their importance. In contrast to promoter CGIs which are predominantly unmethylated, 3UTR CGIs are often methylated. Genes with 3UTR CGIs are associated with several different cancers and cancer-related signalling pathways. Moreover, 3UTR CGIs are differentially methylated in cancers, with changes in methylation associated with changes in gene expression. Together this data suggests the importance of 3UTR CGIs and their methylation in gene expression regulation in cancer.