Zhang Chaolin, Xuan Zhenyu, Otto Stefanie, Hover John R, McCorkle Sean R, Mandel Gail, Zhang Michael Q
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
Nucleic Acids Res. 2006 May 2;34(8):2238-46. doi: 10.1093/nar/gkl248. Print 2006.
Transcription factor binding sites (TFBSs) are short DNA sequences interacting with transcription factors (TFs), which regulate gene expression. Due to the relatively short length of such binding sites, it is largely unclear how the specificity of protein-DNA interaction is achieved. Here, we have performed a genome-wide analysis of TFBS-like sequences for the transcriptional repressor, RE1 Silencing Transcription Factor (REST), as well as for several other representative mammalian TFs (c-myc, p53, HNF-1 and CREB). We find a nonrandom distribution of inexact sites for these TFs, referred to as highly-degenerate TFBSs, that are enriched around the cognate binding sites. Comparisons among human, mouse and rat orthologous promoters reveal that these highly-degenerate sites are conserved significantly more than expected by random chance, suggesting their positive selection during evolution. We propose that this arrangement provides a favorable genomic landscape for functional target site selection.
转录因子结合位点（TFBSs）是与转录因子（TFs）相互作用的短DNA序列，转录因子可调控基因表达。由于这类结合位点相对较短，目前很大程度上尚不清楚蛋白质与DNA相互作用的特异性是如何实现的。在此，我们对转录抑制因子RE1沉默转录因子（REST）以及其他几种代表性的哺乳动物转录因子（c-myc、p53、肝细胞核因子-1（HNF-1）和环磷腺苷效应元件结合蛋白（CREB））的类TFBS序列进行了全基因组分析。我们发现这些转录因子的不精确位点呈非随机分布，即高度简并的TFBSs，它们在同源结合位点周围富集。对人、小鼠和大鼠直系同源启动子的比较表明，这些高度简并的位点的保守性显著高于随机预期，这表明它们在进化过程中受到了正选择。我们认为这种排列为功能性靶位点的选择提供了有利的基因组格局。
