Recruitment of transcription factors to the target site by triplex-forming oligonucleotides

被引:18
|
作者
Svinarchuk, F
Nagibneva, I
Chern, D
AitSiAli, S
Pritchard, LL
Robin, P
Malvy, C
HarelBellan, A
机构
[1] NOVOSIBIRSK BIOORGAN CHEM INST,DEPT BIOCHEM,NOVOSIBIRSK 630090,RUSSIA
[2] INST FEDERATIF CANC,CNRS,UPR 9079,IFC 01,LAB ONCOGENESE DIFFERENCIAT & TRANSDUST SIGNAL,F-94801 VILLEJUIF,FRANCE
[3] INST GUSTAVE ROUSSY,CNRS,URA 147,LAB MICROSCOPIE CELLULAIRE & MOL,F-94805 VILLEJUIF,FRANCE
[4] RUSSIAN ACAD SCI,INST MOL GENET,MOSCOW 123182,RUSSIA
关键词
D O I
10.1093/nar/25.17.3459
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Triplex-forming oligonucleotides (TFOs) are generally designed to inhibit transcription or DNA replication but can be used for more diverse purposes, Here we have designed a hairpin-TFO able to recruit transcription factors to a target DNA, The designed oligonucleotide contains a tripler-forming sequence, linked through a nucleotide loop to a double-stranded hairpin including the SRE enhancer of the c-fos gene promoter, We show here that this oligonucleotide can specifically recognise its DNA target at physiological salt and pH conditions, The stability of the tripler formed under these conditions is very high: >90% of the tripler remains intact after 24 h of incubation. Bound to the double-stranded target DNA, the oligonucleotide retains its ability to interact specifically with transcription factors, recruiting them to the proximity of the target DNA. Our results suggest that this type of oligonucleotide may prove useful in the design of new tools for artificial modulation of gene expression.
引用
收藏
页码:3459 / 3464
页数:6
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