Triplex-forming oligonucleotide target sequences in the human genome

被引:132
作者
Goñi, JR
de la Cruz, X
Orozco, M
机构
[1] Inst Rec Biomed, Mol Modelling & Bioinformat Unit, Barcelona 08028, Spain
[2] Lluis Co, Inst Catalana Ric & Estudis Avancats, Barcelona 08028, Spain
[3] Univ Barcelona, Fac Quim, Dept Bioquim & Biol Mol, E-08028 Barcelona, Spain
关键词
D O I
10.1093/nar/gkh188
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
The existence of sequences in the human genome which can be a target for triplex formation, and accordingly are candidates for anti-gene therapies, has been studied by using bioinformatics tools. It was found that the population of triplex-forming oligonucleotide target sequences (TTS) is much more abundant than that expected from simple random models. The population of TTS is large in all the genome, without major differences between chromosomes. A wide analysis along annotated regions of the genome allows us to demonstrate that the largest relative concentration of TTS is found in regulatory regions, especially in promoter zones, which suggests a tremendous potentiality for triplex strategy in the control of gene expression. The dependence of the stability and selectivity of the triplexes on the length of the TTS is also analysed using knowledge-based rules.
引用
收藏
页码:354 / 360
页数:7
相关论文
共 39 条
[1]   Unambiguous demonstration of triple-helix-directed gene modification [J].
Barre, FX ;
Ait-Si-Ali, S ;
Giovannangeli, C ;
Luis, R ;
Robin, P ;
Pritchard, LL ;
Hélène, C ;
Harel-Bellan, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (07) :3084-3088
[2]   Specificity of antiparallel DNA triple helix formation [J].
Chandler, SP ;
Fox, KR .
BIOCHEMISTRY, 1996, 35 (47) :15038-15048
[3]   A DNA polymorphism discovery resource for research on human genetic variation [J].
Collins, FS ;
Brooks, LD ;
Chakravarti, A .
GENOME RESEARCH, 1998, 8 (12) :1229-1231
[4]   SITE-SPECIFIC OLIGONUCLEOTIDE BINDING REPRESSES TRANSCRIPTION OF THE HUMAN C-MYC GENE INVITRO [J].
COONEY, M ;
CZERNUSZEWICZ, G ;
POSTEL, EH ;
FLINT, SJ ;
HOGAN, ME .
SCIENCE, 1988, 241 (4864) :456-459
[5]   SPECIFIC-INHIBITION OF TRANSCRIPTION BY TRIPLE HELIX-FORMING OLIGONUCLEOTIDES [J].
DUVALVALENTIN, G ;
THUONG, NT ;
HELENE, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (02) :504-508
[6]  
Ebbinghaus SW, 1996, GENE THER, V3, P287
[7]   Targeted inhibition of transcription elongation in cells mediated by triplex-forming oligonucleotides [J].
Faria, M ;
Wood, CD ;
Perrouault, L ;
Nelson, JS ;
Winter, A ;
White, MRH ;
Hélène, C ;
Giovannangeli, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (08) :3862-3867
[8]   FORMATION OF A THREE-STRANDED POLYNUCLEOTIDE MOLECULE [J].
FELSENFELD, G ;
DAVIES, DR ;
RICH, A .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1957, 79 (08) :2023-2024
[9]   Tripler technology takes off [J].
Giovannangeli, C ;
Hélène, C .
NATURE BIOTECHNOLOGY, 2000, 18 (12) :1245-1246
[10]  
GRIGORIEV M, 1992, J BIOL CHEM, V267, P3389