CpG

CpG refers to a dinucleotide consisting of cytosine followed by guanine linked by a phosphodiester bond in DNA. The term is widely used to describe cytosines that precede guanines in the genome, a context that is a major target for DNA methylation in many organisms.

In vertebrates, CpG sites are underrepresented in the bulk genome because methylated cytosines at CpG dinucleotides frequently mutate to thymine through deamination, leading to C to T transitions. Despite this depletion, regions with high CpG density exist and are functionally important.

DNA methylation at CpG dinucleotides is a central epigenetic modification. DNA methyltransferases, including DNMT1 and the de novo DNMT3 family, add a methyl group to the 5-position of cytosine to form 5-methylcytosine. TET enzymes can oxidize 5mC to 5-hydroxymethylcytosine and further oxidation products, enabling potential active demethylation. Methylation status of CpG sites influences gene regulation by affecting transcription factor binding and chromatin structure.

CpG islands are regions rich in CpG dinucleotides, typically located near gene promoters. They are usually GC-rich, with a high observed-to-expected CpG ratio, and are generally unmethylated in healthy somatic cells, though they can become methylated in development, imprinting, or disease.

Importance and applications: CpG methylation patterns play key roles in development, genomic imprinting, X-chromosome inactivation, and disease. Techniques such as bisulfite sequencing and methylation arrays are used to map CpG methylation across the genome.