The 3'-end region of the human PDGFR-β core promoter nuclease hypersensitive element forms a mixture of two unique end-insertion G-quadruplexes

Biochimica Et Biophysica Acta. General Subjects
Buket OnelDanzhou Yang

Abstract

While 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. We use 1D and 2D high-field NMR, in combination with Dimethylsulfate Footprinting, Circular Dichroism Spectroscopy, and Electrophoretic Mobility Shift Assay. We 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...Continue Reading

Citations

Jan 27, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zhi-Yin SunTian-Miao Ou
Aug 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Guanhui WuDanzhou Yang
Nov 15, 2019·Nucleic Acids Research·Betty ChuPaul J Paukstelis
Dec 2, 2020·International Journal of Molecular Sciences·Victoria Sanchez-MartinJose A Garcia-Salcedo
Aug 31, 2021·Cellular and Molecular Life Sciences : CMLS·Fang-Yuan TengYong Xu

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