+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Characterization of the G-quadruplexes in the duplex nuclease hypersensitive element of the PDGF-A promoter and modulation of PDGF-A promoter activity by TMPyP4



Characterization of the G-quadruplexes in the duplex nuclease hypersensitive element of the PDGF-A promoter and modulation of PDGF-A promoter activity by TMPyP4



Nucleic Acids Research 35(22): 7698-7713



The proximal 5'-flanking region of the human platelet-derived growth factor A (PDGF-A) promoter contains one nuclease hypersensitive element (NHE) that is critical for PDGF-A gene transcription. On the basis of circular dichroism (CD) and electrophoretic mobility shift assay (EMSA), we have shown that the guanine-rich (G-rich) strand of the DNA in this region can form stable intramolecular parallel G-quadruplexes under physiological conditions. A Taq polymerase stop assay has shown that the G-rich strand of the NHE can form two major G-quadruplex structures, which are in dynamic equilibrium and differentially stabilized by three G-quadruplex-interactive drugs. One major parallel G-quadruplex structure of the G-rich strand DNA of NHE was identified by CD and dimethyl sulfate (DMS) footprinting. Surprisingly, CD spectroscopy shows a stable parallel G-quadruplex structure formed within the duplex DNA of the NHE at temperatures up to 100 degrees C. This structure has been characterized by DMS footprinting in the double-stranded DNA of the NHE. In transfection experiments, 10 microM TMPyP4 reduced the activity of the basal promoter of PDGF-A approximately 40%, relative to the control. On the basis of these results, we have established that ligand-mediated stabilization of G-quadruplex structures within the PDGF-A NHE can silence PDGF-A expression.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 020712411

Download citation: RISBibTeXText

PMID: 17984069

DOI: 10.1093/nar/gkm538


Related references

Quadruplex-duplex competition in the nuclease hypersensitive element of human c-myc promoter: C to T mutation in C-rich strand enhances duplex association. Biochemical and Biophysical Research Communications 327(1): 49-56, 2005

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 1862(4): 846-854, 2018

An S1 nuclease sensitive region in the PDGF A-chain gene promoter contains a positive transcriptional regulatory element. Biochemical & Biophysical Research Communications. 1: 103-110, 1994

Platination of telomeric sequences and nuclease hypersensitive elements of human c-myc and PDGF-A promoters and their ability to form G-quadruplexes. Febs Journal 276(2): 401-409, 2008

SIS/PDGF-B promoter isolation and characterization of regulatory elements necessary for basal expression of the SIS/PDGF-B gene in U2-OS osteosarcoma cells. Journal of Biological Chemistry 269(46): 28648-28654, 1994

Modulation of human platelet derived growth factor pdgf a chain gene transcription by promoter sites sensitive to s1 nuclease. FASEB Journal 5(4): A818, 1991

Identification and characterization of an activating regulatory element in the human SIS/PDGF-B-promoter. Journal of Cellular Biochemistry Suppl. 0(18C): 48, 1994

Platelet-derived Growth Factor (PDGF) Receptor-a-activated c-Jun NH2-terminal Kinase-1 Is Critical for PDGF-induced p21WAF1/CIP1 Promoter Activity Independent of p53. The Journal of Biological Chemistry 278(49): 582-8, 2003

Platelet-derived growth factor (PDGF) receptor-alpha-activated c-Jun NH2-terminal kinase-1 is critical for PDGF-induced p21WAF1/CIP1 promoter activity independent of p53. Journal of Biological Chemistry 278(49): 49582-8, 2003

Thermodynamic stability and folding kinetics of the major G-quadruplex and its loop isomers formed in the nuclease hypersensitive element in the human c-Myc promoter: effect of loops and flanking segments on the stability of parallel-stranded intramolecular G-quadruplexes. Biochemistry 49(43): 9152-9160, 2010

Sp1 binding site is sensitive to s1 nuclease in the pdgf a chain promoter. Journal of Cell Biology 107(6 Part 3): 91A, 1988

A novel type of regulatory element is required for promoter-specific activity of the PDGF-B intronic enhancer region. Growth Factors 16(2): 137-151, 1998

A Novel Type of Regulatory Element is Required for Promoter-specific Activity of the Pdgf-B Intronic Enhancer Region. Growth Factors 16(2): 137-151, 1998

Tumor promoter enhances mitogenesis by PDGF with little effect on PDGF binding. Journal of Cellular Physiology 126(2): 254-258, 1986

The Consequences of Overlapping G-Quadruplexes and i-Motifs in the Platelet-Derived Growth Factor Receptor β Core Promoter Nuclease Hypersensitive Element Can Explain the Unexpected Effects of Mutations and Provide Opportunities for Selective Targeting of Both Structures by Small Molecules To Downregulate Gene Expression. Journal of the American Chemical Society 139(22): 7456-7475, 2017