CPGs

CpG refers to a dinucleotide in DNA containing cytosine followed by guanine connected by a phosphodiester bond, where the "p" denotes the phosphodiester linkage. CpG sites are targets for DNA methylation in many organisms, where the cytosine is commonly modified to 5-methylcytosine (5mC). In vertebrate genomes, CpG dinucleotides are underrepresented due to the mutagenic deamination of 5mC to thymine, leading to CpG depletion over evolutionary time. However, regions with high CpG density called CpG islands are often located near gene promoters. CpG islands are typically 300-3,000 base pairs long, with high GC content and a high observed-to-expected CpG ratio, and are usually unmethylated in normal cells, correlating with active transcription. Methylation of CpG inside promoter regions is associated with transcriptional silencing, while unmethylated CpGs in promoter CpG islands support gene expression. Genome-wide patterns of CpG methylation are a key epigenetic mechanism, established by de novo methyltransferases DNMT3A/3B and maintained during DNA replication by DNMT1, often heritable through cell divisions. CpG methylation also participates in genomic imprinting and X-chromosome inactivation, and changes in methylation patterns are linked to aging and diseases such as cancer, where promoter CpGs can become hypermethylated and large-scale hypomethylation can occur elsewhere. Additional context includes CpG shores and shelves, regions adjacent to CpG islands with intermediate methylation changes. Detecting CpG methylation commonly uses bisulfite sequencing and related array-based assays.