CpG islands as genomic footprints of promoters that are associated with replication origins

The primary target for DNA methylation in mammalian genomes is cytosine in the dinucleotide CpG. High densities of CpG dinucleotides are found in CpG islands, but paradoxically CpG islands are normally in a non-methylated state. Here, we speculate why CpG islands are immune to methylation and why they are so rich in guanine and cytosine relative to the surrounding DNA. We propose that CpG islands are associated with promoters that are transcriptionally active at totipotent stages of development and can also act as origins of DNA replication. CpG islands may be 'footprints' caused by early DNA replication intermediates at dual function promoters of this kind.