CpG islands (CGIs) are commonly used as genomic markers to study the patterns 
and regulatory consequences of DNA methylation. Interestingly, recent studies 
reveal a substantial diversity among CGIs: long and short CGIs, for example, 
exhibit contrasting patterns of gene expression complexity and nucleosome 
occupancy. Evolutionary origins of CGIs are also highly heterogeneous. In order 
to systematically evaluate potential diversities among CGIs and ultimately to 
illuminate the link between diversity of CGIs and their epigenetic variation, we 
analyzed the nucleotide-resolution DNA methylation maps (methylomes) of multiple 
cellular origins. We discover novel 'clusters' of CGIs according to their 
patterns of DNA methylation; the stably hypomethylated CGI cluster (cluster I), 
sperm-hypomethylated CGI cluster (cluster II), and variably methylated CGI 
cluster (cluster III). These epigenomic CGI clusters are strikingly distinct at 
multiple biological features including genomic, evolutionary, and functional 
characteristics. At the genomic level, the stably hypomethylated CGI cluster 
tends to be longer and harbors many more CpG dinucleotides than those in other 
clusters. They are also frequently associated with promoters, while CGI clusters 
II and III mostly reside in intragenic or intergenic regions and exhibit highly 
tissue-specific DNA methylation. Functional ontology terms and transcriptional 
profiles co-vary with CGI clusters, indicating that the regulatory functions of 
CGIs are tightly linked to their heterogeneity. 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.