ArticleBiochimica et biophysica acta. General subjects2018
The 3'-end region of the human PDGFR-β core promoter nuclease hypersensitive element forms a mixture of two unique end-insertion G-quadruplexes.
Article in Biochimica et biophysica acta. General subjects, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 19 citations in OpenAlex.
- Structures and dynamics of the major G-quadruplex in the human PDGFR-β gene promoter: insights into vacancy G-quadruplex formation.Nucleic acids research · 2026Article
- DNA G-Quadruplex in Human Telomeres and Oncogene Promoters: Structures, Functions, and Small Molecule Targeting.Accounts of chemical research · 2022Article
- Regulation of PDGFR-β gene expression by targeting the G-vacancy bearing G-quadruplex in promoter.Nucleic acids research · 2021Article
- G-quadruplex DNA: a novel target for drug design.Cellular and molecular life sciences : CMLS · 2021Review
- Mechanical diversity and folding intermediates of parallel-stranded G-quadruplexes with a bulge.Nucleic acids research · 2021Article
- An Updated Focus on Quadruplex Structures as Potential Therapeutic Targets in Cancer.International journal of molecular sciences · 2020Review
- Custom G4 Microarrays Reveal Selective G-Quadruplex Recognition of Small Molecule BMVC: A Large-Scale Assessment of Ligand Binding Selectivity.Molecules (Basel, Switzerland) · 2020Article
- PDGFR-β Promoter Forms a Vacancy G-Quadruplex that Can Be Filled in by dGMP: Solution Structure and Molecular Recognition of Guanine Metabolites and Drugs.Journal of the American Chemical Society · 2020Article
- Article
- A DNA G-quadruplex/i-motif hybrid.Nucleic acids research · 2019Article
- Developing Novel G-Quadruplex Ligands: from Interaction with Nucleic Acids to Interfering with Nucleic Acid⁻Protein Interaction.Molecules (Basel, Switzerland) · 2019Review
- G-Quadruplex DNA and RNA.Methods in molecular biology (Clifton, N.J.) · 2019Article
- NMR structure study of DNA G-quadruplexes and ligand complexes.Progress in nuclear magnetic resonance spectroscopyReview
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5 authors at 5 institutions in 1 country.
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Abstract
backgroundWhile the most stable G-quadruplex formed in the human PDGFR-β promoter nuclease hypersensitive element (NHE) is the 5'-mid G-quadruplex, the 3'-end sequence that contains a 3'-GGA run forms a less stable G-quadruplex. Recently, the 3'-end G-quadruplex was found to be a transcriptional repressor and can be selectively targeted by a small molecule for PDGFR-β downregulation.
methodWe use 1D and 2D high-field NMR, in combination with Dimethylsulfate Footprinting, Circular Dichroism Spectroscopy, and Electrophoretic Mobility Shift Assay.
resultsWe determine that the PDGFR-β extended 3'-end NHE sequence forms two novel end-insertion intramolecular G-quadruplexes that co-exist in equilibrium under physiological salt conditions. One G-quadruplex has a 3'-non-adjacent flanking guanine inserted into the 3'-external tetrad (3'-insertion-G4), and another has a 5'-non-adjacent flanking guanine inserted into the 5'-external tetrad (5'-insertion-G4). The two guanines in the GGA-run move up or down within the G-quadruplex to accommodate the inserted guanine. Each end-insertion G-quadruplex has a low thermal stability as compared to the 5'-mid G-quadruplex, but the selective stabilization of GSA1129 shifts the equilibrium toward the 3'-end G-quadruplex in the PDGFR-β NHE.
conclusionAn equilibrium mixture of two unique end-insertion intramolecular G-quadruplexes forms in the PDGFR-β NHE 3'-end sequence that contains a GGA-run and non-adjacent guanines in both the 3'- and 5'- flanking segments; the novel end-insertion structures of the 3'-end G-quadruplex are selectively stabilized by GSA1129. GENERAL SIGNIFICANCE: We show for the first time that an equilibrium mixture of two unusual end-insertion G-quadruplexes forms in a native promoter sequence and appears to be the molecular recognition for PDGFR-β downregulation.
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