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PMID: 7687346 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Inhibition of gene transcription by purine rich triplex forming oligodeoxyribonucleotides.

Nucleic acids research ·Vol. 21 ·No. 12 ·1993-06-25 ·Pages 2845-52

Roy C

Abstract

Several oligodeoxynucleotides (ODNs) were designed in order to interact with the purine rich element of the IRE (Interferon Responsive Element) of the 6-16 gene by triplex formation. An ODN of 21 bases, the sequence being identical to that of the purine strand of the IRE (48% G), but in reverse orientation, was able to interact with the IRE (KD: 20 nM). The binding was Mg2+ dependent. The two purine strands of the triplex were oriented antiparallel as confirmed by DNAase I and copper-phenanthroline footprinting experiments. An ODN in which A were replaced by T, also interacted with the same target, but with a lower affinity. Exonuclease III action indicated that the two IRE repeats of the 6-16 promoter interacted with each other through Hoogsteen base pairing, the third strand being parallel to the paired Watson-Crick strand. This led to a potential H-DNA structure which could be destabilized by adding ODNs able to form a triplex structure. 6-16 IRE driven-reporter gene constructs lost their interferon stimulability when co-transfected with triplex forming ODNs. The range of effective ODN concentrations was compatible with the affinity determined when measuring their direct interactions with the DNA.

MeSH Terms
Base Sequence Binding Sites DNA/chemistry,genetics,metabolism Deoxyribonuclease I Interferons/pharmacology Magnesium/pharmacology Molecular Sequence Data Nucleic Acid Conformation Oligodeoxyribonucleotides/chemistry,metabolism,pharmacology Phenanthrolines Plasmids Purines/chemistry Structure-Activity Relationship Transcription, Genetic/drug effects Transfection
Chemicals
Oligodeoxyribonucleotides Phenanthrolines Purines DNA Interferons Deoxyribonuclease I Magnesium 1,10-phenanthroline
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Roy C
Institut de Génétique Moléculaire, UMR 9942, CNRS, Montpellier, France.
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45 references, click to expand
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/21.12.2845
Published
1993-06-25
Pages
2845-52
Language
English
Region
England
NLM ID
0411011
PMCID
PMC309666
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/21.12.2845 PMC Full Text View journal details
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