G-quadruplexes in promoters throughout the human genome

By Julian Leon Huppert, Shankar Balasubramanian. Nucleic Acids Research, 2006

1,260 citations recorded by the source corpus.

Certain G-rich DNA sequences readily form four-stranded structures called G-quadruplexes. These sequence motifs are located in telomeres as a repeated unit, and elsewhere in the genome, where their function is currently unknown. It has been proposed that G-quadruplexes may be directly involved in gene regulation at the level of transcription. In support of this hypothesis, we show that the promoter regions (1 kb upstream of the transcription start site TSS) of genes are significantly enriched in quadruplex motifs relative to the rest of the genome, with >40% of human gene promoters containing one or more quadruplex motif. Furthermore, these promoter quadruplexes strongly associate with nuclease hypersensitive sites identified throughout the genome via biochemical measurement. Regions of the human genome that are both nuclease hypersensitive and within promoters show a remarkable (230-fold) enrichment of quadruplex elements, compared to the rest of the genome. These quadruplex motifs identified in promoter regions also show an interesting structural bias towards more stable forms. These observations support the proposal that promoter G-quadruplexes are directly involved in the regulation of gene expression.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/1ba10782d6e7de8c36f8e395b4774593f27da8bf

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Citations in the corpus

G-quadruplexes and their regulatory roles in biology (2015, background): “Interestingly, pG4s are more frequent in oncogenes or regulatory genes than in house keeping, or tumour suppressor genes (88,89), (for review (9,84)).”
Human telomere, oncogenic promoter and 5′-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics (2007, background): “In addition, it has recently been shown that promoter regions spanning 1 kb upstream of transcription start sites of genes are significantly enriched in putative G-quadruplex-forming motifs and that these putative promoter G-quadruplexforming regions strongly associate with nuclease hypersensitivity”
Targeting G-quadruplexes in gene promoters: a novel anticancer strategy? (2011, methodology): “Various G-quadruplex search algorithms have been published, ranging from those that use more explicit definitions of nucleotide arrangements (for example, GGG 3+ N 1–7 GGG 3+ N 1–7 GGG 3+ N 1–7 GGG 3+ N 1–7”
Stability and kinetics of G-quadruplex structures (2008, background): “gen bonds in nucleic acid base pairs by internucleotide (2)J(NN)”