Rivas María Luisa, Cobreros Laura, Zeidler Martin P, Hombría James Castelli-Gair
Centro Andaluz de Biología del Desarrollo, CSIC/UPO, Universidad Pablo de Olavide, Carretera de Utrera km 1, 41013 Seville, Spain.
EMBO Rep. 2008 Nov;9(11):1114-20. doi: 10.1038/embor.2008.170. Epub 2008 Sep 19.
In vertebrates, seven signal transducer and activator of transcription (STAT) proteins bind to palindromic sites separated by spacers of two or three nucleotides (STAT1), four nucleotides (STAT6) or three nucleotides (STAT2 to STAT5a/b). This diversity of binding sites provides specificity to counter semiredundancy and was thought to be a recent evolutionary acquisition. Here, we examine the natural DNA-binding sites of the single Drosophila Stat and show that this is not the case. Rather, Drosophila Stat92E is able to bind to and activate target gene expression through both 3n and 4n spaced sites. Our experiments indicate that Stat92E has a higher binding affinity for 3n sites than for 4n sites and suggest that the levels of target gene expression can be modulated by insertion and/or deletion of single bases. Our results indicate that the ancestral STAT protein had the capacity to bind to 3n and 4n sites and that specific STAT binding preferences evolved with the radiation of the vertebrate STAT family.
在脊椎动物中，七种信号转导及转录激活因子（STAT）蛋白可结合到由两或三个核苷酸间隔（STAT1）、四个核苷酸间隔（STAT6）或三个核苷酸间隔（STAT2至STAT5a/b）隔开的回文位点。这种结合位点的多样性为应对半冗余提供了特异性，并且曾被认为是近期的进化获得。在此，我们研究了果蝇中单个Stat的天然DNA结合位点，结果表明并非如此。相反，果蝇Stat92E能够通过3n和4n间隔的位点结合并激活靶基因表达。我们的实验表明，Stat92E对3n位点的结合亲和力高于对4n位点的结合亲和力，并表明靶基因表达水平可通过单个碱基的插入和/或缺失来调节。我们的结果表明，祖先STAT蛋白具有结合3n和4n位点的能力，并且特定的STAT结合偏好随着脊椎动物STAT家族的辐射而进化。
