G-quadruplexes in promoters throughout the human genome
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TLDR
It is shown 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 quadruplexaterials.Abstract:
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.read more
Citations
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Origins and functional impact of copy number variation in the human genome
Donald F. Conrad,Dalila Pinto,Richard Redon,Richard Redon,Lars Feuk,Lars Feuk,Omer Gokcumen,Yujun Zhang,Jan Aerts,T. Daniel Andrews,Chris P. Barnes,Peter J. Campbell,Tomas W Fitzgerald,Min Hu,Chun Hwa Ihm,K. Kristiansson,Daniel G. MacArthur,Jeffrey R. MacDonald,Ifejinelo Onyiah,Andy Wing Chun Pang,Samuel Robson,Kathy Stirrups,Armand Valsesia,Klaudia Walter,John Wei,Chris Tyler-Smith,Nigel P. Carter,Charles Lee,Stephen W. Scherer,Stephen W. Scherer,Matthew E. Hurles +30 more
TL;DR: It is concluded that the heritability void left by genome-wide association studies will not be accounted for by common CNVs, and 30 loci with CNVs that are candidates for influencing disease susceptibility are identified.
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Targeting G-quadruplexes in gene promoters: a novel anticancer strategy?
TL;DR: The evidence for G-quadruplexes in gene promoters is described and their potential as therapeutic targets are discussed, as well as progress in the development of strategies to harness this potential through intervention with small-molecule ligands.
Journal ArticleDOI
DNA secondary structures: stability and function of G-quadruplex structures
TL;DR: This Review focuses on emerging evidence relating to the characteristics of G-quadruplex structures and the possible influence of such structures on genomic stability and cellular processes, such as transcription.
Journal ArticleDOI
G-quadruplexes and their regulatory roles in biology.
Daniela Rhodes,Hans J. Lipps +1 more
TL;DR: Recent evidence for the in vivo presence and function of DNA and RNA G-quadruplexes in various cellular pathways including DNA replication, gene expression and telomere maintenance is summarized.
Journal ArticleDOI
Human telomere, oncogenic promoter and 5′-UTR G-quadruplexes: diverse higher order DNA and RNA targets for cancer therapeutics
TL;DR: The review highlights recent solution NMR-based G-quadruplex structures formed by the four-repeat human telomere in K+ solution and the guanine-rich strands of c-myc, c-kit and variant bcl-2 oncogenic promoters, as well as a bimolecular G- quadruplex that targets HIV-1 integrase.
References
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Structure and function of telomeres
TL;DR: The DNA of telomeres—the terminal DNA-protein complexes of chromosomes—differs notably from other DNA sequences in both structure and function, and has been shown to be essential for telomere maintenance and long-term viability.
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TL;DR: This survey focuses on the folding and structural features on quadruplexes formed from telomeric and non-telomeric DNA sequences, and examines fundamental aspects of topology and the emerging relationships with sequence.
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Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription.
TL;DR: The principle that c-MYC transcription can be controlled by ligand-mediated G-quadruplex stabilization is established, establishing the principle that the purine-rich strand of the DNA in this region can form two different intramolecular G- quadruplex structures.
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Structure and function of telomeres
TL;DR: The history and present situation of Spanish language, culture, literature, cuisine, tourism, and more are explored in more detail in this booklet.
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Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis
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TL;DR: It is speculated that this self-recognition of guanine-rich motifs of DNA serves to bring together, and to zipper up in register, the four homologous chromatids during meiosis.