Cheremushkin E, Kel A
Institute of Cytology & Genetics SB RAN, 10 Lavrentyev pr., 630090, Novosibirsk, Russia.
Pac Symp Biocomput. 2003:291-302. doi: 10.1142/9789812776303_0028.
Phylogenetic footprinting is an efficient approach for revealing potential transcription factor binding sites in promoter sequences. The idea is based on an assumption that functional sites in promoters should evolve much slower then other regions that do not bear any conservative function. Therefore, potential transcription factor (TF) binding sites that are found in the evolutionally conservative regions of promoters have more chances to be considered as "real" sites. The most difficult step of the phylogenetic footprinting is alignment of promoter sequences between different organisms (fe. human and mouse). The conventional alignment methods often can not align promoters due to the high level of sequence variability. We have developed a new alignment method that takes into account similarity in distribution of potential binding sites (motif-based alignment). This method has been used effectively for promoter alignment and for revealing new potential binding sites for various transcription factors. We made a systematic phylogenetic footprinting of human/mouse conserved non-coding sequences (CNS). 60 thousand potential binding sites were revealed in human and mouse genomes. We have developed a database of the predicted potential TF binding sites.
http://compel.bionet.nsc.ru/FunSite/footprint/; www.gene-regulation.com/.
系统发育足迹法是一种在启动子序列中揭示潜在转录因子结合位点的有效方法。该方法基于这样一种假设:启动子中的功能位点进化速度应比其他不具有保守功能的区域慢得多。因此,在启动子进化保守区域中发现的潜在转录因子(TF)结合位点更有可能被视为“真实”位点。系统发育足迹法最困难的步骤是不同生物体(如人类和小鼠)之间启动子序列的比对。由于序列变异性高,传统的比对方法常常无法对启动子进行比对。我们开发了一种新的比对方法,该方法考虑了潜在结合位点分布的相似性(基于基序的比对)。此方法已有效地用于启动子比对以及揭示各种转录因子的新潜在结合位点。我们对人类/小鼠保守非编码序列(CNS)进行了系统的系统发育足迹分析。在人类和小鼠基因组中发现了6万个潜在结合位点。我们建立了一个预测的潜在TF结合位点数据库。
http://compel.bionet.nsc.ru/FunSite/footprint/;www.gene-regulation.com/。