CpGsites

CpG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence, connected by a phosphate bond. The term “CpG” reflects the dinucleotide on the same strand, and such sites are widespread throughout the genome, with particular clustering in certain regions.

In many organisms, including humans, the cytosine within CpG dinucleotides can be modified by methylation to form 5-methylcytosine. DNA methyltransferases, such as DNMT1, DNMT3A, and DNMT3B, establish and maintain these marks. The methylation state of CpG sites is a key epigenetic signal that influences gene expression: methylation in promoter-associated CpG sites or CpG islands is usually associated with transcriptional repression, while unmethylated CpG islands are common in active housekeeping genes. Methylated CpG sites are enriched in repetitive elements and regions that help suppress transposable elements, contributing to genome stability.

CpG islands are genomic regions with a high density of CpG sites and a relatively high GC content. They are often located near gene promoters and are typically unmethylated in normal cells, allowing gene transcription. Outside CpG islands, CpG dinucleotides are more prone to mutation due to deamination of 5-methylcytosine to thymine, leading to a gradual loss of CpG sites over evolutionary time.

Alterations in CpG methylation patterns are associated with development, aging, imprinting disorders, and various diseases, including cancer. CpG site analysis is central to many epigenetic studies, using methods such as bisulfite sequencing, MeDIP, and array-based assays to map methylation at single-base resolution.