CpGdinukleotidides

CpG dinucleotides refer to a sequence of a cytosine nucleotide followed immediately by a guanine nucleotide in a DNA molecule. The 'p' in CpG represents the phosphodiester bond that links the two nucleotides. In vertebrate DNA, CpG dinucleotides are relatively rare compared to their expected frequency. This underrepresentation is primarily due to the spontaneous deamination of cytosine to thymine. If the cytosine in a CpG dinucleotide is methylated (forming 5-methylcytosine), this deamination results in a transition to thymine, effectively creating a TpG dinucleotide and eliminating the CpG sequence.

This methylation of cytosines within CpG dinucleotides is a significant epigenetic modification. It plays a crucial role in regulating gene expression, often leading to gene silencing when occurring in promoter regions. CpG islands, which are regions of DNA with a high frequency of CpG dinucleotides, are often found upstream of gene promoters. The methylation status of these CpG islands can determine whether a gene is actively transcribed or repressed.

Despite the general rarity of CpG dinucleotides in the genome, unmethylated CpG sequences are abundant in the DNA of bacteria and viruses. Consequently, vertebrate immune systems have evolved to detect these unmethylated CpG motifs. Toll-like receptor 9 (TLR9) is a key receptor that recognizes unmethylated CpG DNA, triggering innate immune responses. This recognition mechanism highlights the evolutionary interplay between host defense and the epigenetic landscape of their own genome.