The study investigates the prevalence and functional significance of G-quadruplexes in promoter regions of human genes. G-rich DNA sequences can form four-stranded structures called G-quadruplexes, which are known to occur in telomeres and may play a role in gene regulation. The authors found that promoter regions (1 kb upstream of the transcription start site) of genes are significantly enriched in quadruplex motifs, with over 40% of human gene promoters containing one or more quadruplex motif. These promoter quadruplexes are strongly associated with nuclease hypersensitive sites, and regions of the genome that are both nuclease hypersensitive and within promoters show a 230-fold enrichment of quadruplex elements compared to the rest of the genome. The quadruplex motifs in promoter regions also exhibit a structural bias towards more stable forms, suggesting that they may function as cis-acting regulatory elements. The findings support the hypothesis that promoter G-quadruplexes are directly involved in gene expression regulation.The study investigates the prevalence and functional significance of G-quadruplexes in promoter regions of human genes. G-rich DNA sequences can form four-stranded structures called G-quadruplexes, which are known to occur in telomeres and may play a role in gene regulation. The authors found that promoter regions (1 kb upstream of the transcription start site) of genes are significantly enriched in quadruplex motifs, with over 40% of human gene promoters containing one or more quadruplex motif. These promoter quadruplexes are strongly associated with nuclease hypersensitive sites, and regions of the genome that are both nuclease hypersensitive and within promoters show a 230-fold enrichment of quadruplex elements compared to the rest of the genome. The quadruplex motifs in promoter regions also exhibit a structural bias towards more stable forms, suggesting that they may function as cis-acting regulatory elements. The findings support the hypothesis that promoter G-quadruplexes are directly involved in gene expression regulation.