CABD, CSIC/Universidad Pablo de Olavide, Seville, Spain.
Dev Biol. 2010 Apr 15;340(2):571-82. doi: 10.1016/j.ydbio.2010.02.015. Epub 2010 Feb 18.
The ventral veinless (vvl) and trachealess (trh) genes are determinants of the Drosophila trachea. Early in development both genes are independently activated in the tracheal primordia by signals that are ill defined. Mutants blocking JAK/STAT signaling at any level do not form a tracheal tree suggesting that STAT92E may be an upstream transcriptional activator of the early trachea determinants. To test this hypothesis we have searched for STAT92E responsive enhancers activating the expression of vvl and trh in the tracheal primordia. We show that STAT92E regulated enhancers can be rapidly and efficiently isolated by focusing the analysis on genomic regions with clusters of putative STAT binding sites where at least some of them are phylogenetically conserved. Detailed analysis of a vvl early tracheal enhancer shows that non-conserved sites collaborate with conserved sites for enhancer activation. We find that STAT92E regulated enhancers can be located as far 60 kb from the promoters. Our results indicate that vvl and trh are independently activated by STAT92E which is the most important transcription factor required for trachea specification.
腹侧无脉（vvl）和无气管（trh）基因是果蝇气管的决定因素。在发育早期，这两个基因都被未明确定义的信号独立激活在气管原基中。阻断 JAK/STAT 信号通路的任何水平的突变体都不能形成气管树，这表明 STAT92E 可能是早期气管决定因素的上游转录激活因子。为了验证这一假说，我们已经搜索了 STAT92E 响应增强子，以激活 vvl 和 trh 在气管原基中的表达。我们表明，STAT92E 调节的增强子可以通过将分析集中在具有假定 STAT 结合位点簇的基因组区域上来快速有效地分离，其中至少一些在系统发育上是保守的。对 vvl 早期气管增强子的详细分析表明，非保守位点与保守位点一起协同激活增强子。我们发现，STAT92E 调节的增强子可以位于启动子 60kb 之外。我们的结果表明，vvl 和 trh 是由 STAT92E 独立激活的，STAT92E 是气管特化所必需的最重要的转录因子。
