Goñi J Ramon, de la Cruz Xavier, Orozco Modesto
Molecular Modelling and Bioinformatics Unit, Institut de Recerca Biomédica, Parc Científic de Barcelona, Josep Samitier 1-5, Barcelona 08028, Spain.
Nucleic Acids Res. 2004 Jan 15;32(1):354-60. doi: 10.1093/nar/gkh188. Print 2004.
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.
利用生物信息学工具对人类基因组中可作为三链体形成靶点、因而可作为抗基因治疗候选靶点的序列的存在情况进行了研究。结果发现，形成三链体的寡核苷酸靶序列（TTS）群体比简单随机模型预期的要丰富得多。TTS群体在整个基因组中都很多，染色体之间没有重大差异。对基因组注释区域进行的广泛分析使我们能够证明，TTS的最大相对浓度出现在调控区域，尤其是启动子区域，这表明三链体策略在基因表达控制方面具有巨大潜力。还利用基于知识的规则分析了三链体的稳定性和选择性对TTS长度的依赖性。
