.....We show that CGIs in the human genome are clearly divided into several distinctive clusters based on variable patterns of DNA methylation. Moreover, these epigenomic CGI clusters are strikingly distinct at genomic features. In particular, the stably hypomethylated CGI cluster tends to be longer and harbors larger numbers of CpG dinucleotides than CGIs exhibiting variable DNA methylation. They are also frequently associated with promoters, while CGIs in intragenic or intergenic regions exhibit high tissue-specific DNA methylation. Furthermore, the regulatory functions of CGIs appear to be tightly linked to this uncovered diversity, as evidenced by the co-variation between DNA methylation and functional ontology terms and transcriptional profiles.
Finally, CGIs associated with distinctive biological processes, such as diseases, aging, and imprinting, occur disproportionately across CGI clusters
. These new findings provide an effective means to combine existing knowledge on CGIs into a genomic context while bringing new insights that elucidate the significance of DNA methylation across different biological conditions and demography.