Genome-wide CpG site (CpG sites)

Genome-wide CpG sites are specific regions of the genome where a cytosine nucleotide is followed by a guanine nucleotide, serving as the primary substrate for DNA methylation (Jones, 2012). This epigenetic modification, mediated by DNA methyltransferases (DNMTs), plays a critical role in regulating gene expression, maintaining chromosomal stability, and directing cellular differentiation (Baylin & Jones, 2011). In healthy cells, CpG sites within promoter regions, known as CpG islands, are typically unmethylated to allow for active gene transcription, while those in repetitive elements are methylated to ensure genomic integrity (Robertson, 2005). Aberrant methylation patterns at these sites are a hallmark of various diseases, particularly cancer, where global hypomethylation and site-specific hypermethylation of tumor suppressor genes occur (Laird, 2003). While CpG sites themselves are not traditional protein targets, they are the functional focus of hypomethylating agents like azacitidine and decitabine, which inhibit DNMTs to restore normal transcriptional activity (Gnyszka et al., 2013). Monitoring the methylation status of these sites serves as a vital biomarker for disease progression, aging, and therapeutic response in clinical settings (Horvath, 2013).

Other names

CpG dinucleotidesCG sitesDNA methylation sites5'-C-phosphate-G-3' sitesMethylome

Drugs typically target DNA methyltransferases (DNMTs) to inhibit the covalent addition of methyl groups to cytosine residues at these sites, thereby reversing epigenetic gene silencing.