Methylated CpG dinucleotides in genomic DNA (5mCpG)

Methylated CpG dinucleotides represent a fundamental epigenetic modification in the mammalian genome, involving the addition of a methyl group to the 5th carbon of the cytosine ring within a cytosine-guanine sequence [1]. This process is mediated by DNA methyltransferases (DNMTs) and is essential for maintaining genomic stability, regulating gene expression, and ensuring proper embryonic development [2]. In a healthy state, methylation at promoter-associated CpG islands typically leads to stable gene silencing, whereas global hypomethylation is common in repetitive elements [1]. However, in many diseases, particularly cancer, this landscape is disrupted, often resulting in the hypermethylation of tumor suppressor gene promoters and the silencing of their protective functions [4]. Therapeutic strategies targeting this modification utilize hypomethylating agents, such as azacitidine and decitabine, which inhibit DNMT activity to restore normal gene expression patterns [3]. Beyond oncology, DNA methylation patterns serve as critical biomarkers for aging and various complex diseases, making them a central focus of epigenetic research and diagnostics [2, 4].

Other names

5-methylcytosine5mCDNA methylationCpG methylationMethylated DNA

Drugs targeting methylated CpG sites primarily act as DNA methyltransferase (DNMT) inhibitors; these agents are incorporated into DNA during replication and covalently trap DNMT enzymes, leading to their degradation and subsequent global DNA hypomethylation, which reactivates silenced tumor suppressor genes [3, 4].