CpG islands (CGIs) are short, GC-rich DNA sequences that are predominantly unmethylated and serve as sites of transcription initiation. They are characterized by their elevated G:C content, low CpG depletion, and frequent absence of DNA methylation. CGIs are associated with approximately 70% of annotated gene promoters, including housekeeping genes, tissue-specific genes, and developmental regulator genes. Recent studies have identified a large number of CGIs that are remote from annotated transcription start sites (TSSs) but still function as promoters. These findings highlight the strong correlation between CGIs and transcription initiation. CGIs are distinct from the bulk genomic DNA due to their lack of DNA methylation and CpG deficiency. In vertebrates, the persistence of discrete regions with different DNA methylation states has partitioned DNA sequences into methylated and nonmethylated fractions. CGIs are conserved in both number and genomic location between different vertebrates, suggesting their functional importance. CGIs exhibit a characteristic chromatin structure that predisposes them to promoter activity. They are nucleosome-deficient, enriched in histone H3 and H4 acetylation, and marked by H3K4me3, a signature of active promoters. In contrast, DNA methylation is associated with stable long-term silencing of CGI promoters, often mediated by methyl-binding domain (MBD) proteins that recruit chromatin-modifying activities. Polycomb group proteins (PcG) can also silence CGI promoters, and CGIs may play a role in polycomb recruitment. The methylation-free state of CGIs is crucial for their function as promoters. Transcription factors and transcription itself are believed to be involved in maintaining this state. CGIs are generally protected from de novo DNA methylation, possibly through mechanisms involving 5-hydroxymethylcytosine (hmC) or other factors that prevent DNA methyltransferase activity. In conclusion, CGIs are genomic platforms for regulating transcription at their associated promoters. Their unique DNA sequence features, such as CpG richness and high G+C content, contribute to their regulatory functions. The coexistence of active and inactive chromatin structures at bivalent CGIs may facilitate decisive switching between transcriptional activity and silencing.CpG islands (CGIs) are short, GC-rich DNA sequences that are predominantly unmethylated and serve as sites of transcription initiation. They are characterized by their elevated G:C content, low CpG depletion, and frequent absence of DNA methylation. CGIs are associated with approximately 70% of annotated gene promoters, including housekeeping genes, tissue-specific genes, and developmental regulator genes. Recent studies have identified a large number of CGIs that are remote from annotated transcription start sites (TSSs) but still function as promoters. These findings highlight the strong correlation between CGIs and transcription initiation. CGIs are distinct from the bulk genomic DNA due to their lack of DNA methylation and CpG deficiency. In vertebrates, the persistence of discrete regions with different DNA methylation states has partitioned DNA sequences into methylated and nonmethylated fractions. CGIs are conserved in both number and genomic location between different vertebrates, suggesting their functional importance. CGIs exhibit a characteristic chromatin structure that predisposes them to promoter activity. They are nucleosome-deficient, enriched in histone H3 and H4 acetylation, and marked by H3K4me3, a signature of active promoters. In contrast, DNA methylation is associated with stable long-term silencing of CGI promoters, often mediated by methyl-binding domain (MBD) proteins that recruit chromatin-modifying activities. Polycomb group proteins (PcG) can also silence CGI promoters, and CGIs may play a role in polycomb recruitment. The methylation-free state of CGIs is crucial for their function as promoters. Transcription factors and transcription itself are believed to be involved in maintaining this state. CGIs are generally protected from de novo DNA methylation, possibly through mechanisms involving 5-hydroxymethylcytosine (hmC) or other factors that prevent DNA methyltransferase activity. In conclusion, CGIs are genomic platforms for regulating transcription at their associated promoters. Their unique DNA sequence features, such as CpG richness and high G+C content, contribute to their regulatory functions. The coexistence of active and inactive chromatin structures at bivalent CGIs may facilitate decisive switching between transcriptional activity and silencing.