Genomic DNA at CpG sequences (CpG) (CpG)

Genomic DNA at CpG sequences refers to specific regions of the genome where a cytosine nucleotide is followed by a guanine nucleotide in the 5' to 3' direction (Bird, 2002). These sites are frequently clustered into CpG islands located within or near the promoter regions of approximately 70% of human genes (Gardiner-Garden & Frommer, 1987). The methylation of cytosine at these sites is a primary epigenetic mechanism used to regulate gene expression, maintain genomic stability, and manage X-chromosome inactivation (Bird, 2002). In many diseases, particularly cancer, aberrant hypermethylation of CpG islands leads to the transcriptional silencing of tumor suppressor genes, contributing to tumor progression (Baylin & Jones, 2011). Therapeutic agents known as hypomethylating agents, such as azacitidine and decitabine, target these sites by inhibiting the enzymes responsible for maintaining methylation (Gnyszka et al., 2013). By preventing the addition of methyl groups, these drugs facilitate the reactivation of silenced genes and can induce cell differentiation or apoptosis in malignant cells (NIH/NCI). Furthermore, the methylation status of specific CpG sites serves as a critical biomarker for cancer diagnosis, prognosis, and the determination of biological age (Horvath, 2013).

Other names

CpG sitesCpG islands5'-C-phosphate-G-3' sitesCytosine-phosphodiester-Guanine sitesDNA methylation sites

Hypomethylating agents act as cytosine analogs that incorporate into DNA during replication and irreversibly bind DNA methyltransferases (DNMTs), preventing the methylation of cytosine at CpG sites and restoring gene expression (Gnyszka et al., 2013; NIH).