CpG islands in the genome: their structure, type, function and evolutionary characteristics

The content of CpG dinucleotides is depleted in the mammalian genome due to deamination of methylated cytosine, and this process is a repressive signal that leads to long-term gene silencing. However, CG reduction does not occur in all genomic regions. It has been reported that the mammalian genome cantains regions of the DNA sequence, known as CpG islands (CGIs), with a high GC base composition and a high density of CpG dinucleotides relative to the bulk genome. The CpG islands usually remain hypometylated in the majority of annotated genes. CGIs have a high presence in the promoters and first exons of the gene, and therefore, act as hubs regulating gene expression and transcription start sites. In fact, most CGIs are found in transcription start sites and approximately 70% of annotated gene promoters, including almost all housekeeping genes, as well as some tissue-specific and regulatory genes. However, CGI methylation, as a heritable epigenetic mark, can occur in somatic tissues, leading to gene silencing such as an X-inactivation and genomic imprinting. In addition, differential methylation has been observed between tissues. It means DNA methylation play an important role in the regulation of gene expression during cell specifications. Based on genome annotations, almost half of identified CGIs, known as orphan CGI, are located either whithin genes (intragenic) or distal to genes (intergenic).