Inhibition of interleukin-2 receptor alpha-subunit gene expression by oligonucleotide-directed triple helix formation.
Oligonucleotide-directed triple helix formation represents a promising approach to block gene expression at the transcriptional level. We have previously shown [10] that a triple-helix-forming oligonucleotide was able to inhibit promoter function of reporter constructs in live cells, provided that the oligonucleotide was covalently linked to an intercalating agent which stabilizes triple-helical complexes. In order to demonstrate that this inhibitory effect was due to triple helix formation, we have mutated the oligonucleotide target site in the promoter of the interleukin-2 receptor alpha-chain gene. The mutated version of the promoter does not bind, and is not inhibited by the oligonucleotide, demonstrating that the observed inhibition of the wild-type promoter is indeed due to triple helix formation within cells.
Grigoriev
M
M
Laboratoire de Biologie des Tumeurs Humaines, URA 1156, Institut Gustave Roussy, Villejuif, France.
Praseuth
D
D
Guieysse
A L
AL
Robin
P
P
Thuong
N T
NT
Hélène
C
C
Harel-Bellan
A
A
D015870:Gene Expression / Q000187:drug effects*; D066298:In Vitro Techniques; D016328:NF-kappa B / Q000235:genetics; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics*
D016328:NF-kappa B; D009841:Oligonucleotides; D015375:Receptors, Interleukin-2