methylCpG

MethylCpG refers to a methylated cytosine within a CpG dinucleotide in DNA, typically described as 5-methylcytosine (5mC). In vertebrates, CpG sites are usually methylated, though regions known as CpG islands—often located at gene promoters—tend to be unmethylated in normal cells to permit transcription. DNA methylation is a key epigenetic mark that influences chromatin structure and gene expression.

Methylation patterns are established by DNA methyltransferases. DNMT3A and DNMT3B perform de novo methylation, setting new marks, while DNMT1 maintains existing methylation patterns during DNA replication. Demethylation can occur through pathways involving TET enzymes, which oxidize 5mC to forms such as 5-hydroxymethylcytosine, enabling active or passive demethylation.

Methyl-CpG binding domain (MBD) proteins, including MeCP2 and MBD1–4, recognize methyl-CpG sites and recruit co-repressor complexes that modify histones to repress transcription. Thus methylCpG acts as a signal that can suppress gene activity, stabilize cell identity, and participate in imprinting and X-chromosome inactivation.

Dysregulation of methylCpG is linked to development, aging, and disease. Promoter hypermethylation can silence tumor suppressor genes in cancer, while global hypomethylation may contribute to genomic instability. The spontaneous deamination of 5mC to thymine also generates C>T mutations, shaping mutational landscapes in tumors.

Detection methods include bisulfite sequencing (gold standard) and enrichment-based approaches like MeDIP-seq or whole-genome bisulfite sequencing, which map methylation at base-pair resolution or genome-wide.

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