Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Cell Rep. 2019 Feb 26;26(9):2407-2418.e5. doi: 10.1016/j.celrep.2019.01.115.
Transcription of developmental genes is controlled by multiple enhancers. Frequently, more than one enhancer can activate transcription from the same promoter in the same cells. How is regulatory information from multiple enhancers combined to determine the overall expression output? We measure nascent transcription driven by a pair of shadow enhancers, each enhancer of the pair separately, and each duplicated, using live imaging in Drosophila embryos. This set of constructs allows us to quantify the input-output function describing signal integration by two enhancers. We show that signal integration performed by these shadow enhancers and duplications varies across the expression pattern, implying that how their activities are combined depends on the transcriptional regulators bound to the enhancers in different parts of the embryo. Characterizing signal integration by multiple enhancers is a critical step in developing conceptual and computational models of gene expression at the locus level, where multiple enhancers control transcription together.
发育基因的转录由多个增强子控制。通常，一个以上的增强子可以在相同的细胞中从同一个启动子激活转录。那么，多个增强子的调控信息是如何结合起来确定整体表达输出的呢？我们使用活体成像技术在果蝇胚胎中测量了一对影子增强子驱动的新生转录，每个增强子单独驱动，每个增强子都进行了复制。这组构建体使我们能够定量描述由两个增强子进行的信号整合的输入-输出函数。我们表明，这些影子增强子和复制体的信号整合在表达模式上存在差异，这意味着它们的活性如何结合取决于在胚胎不同部位与增强子结合的转录调节因子。对多个增强子的信号整合进行表征是在基因表达的局部水平上构建概念和计算模型的关键步骤，在该水平上，多个增强子共同控制转录。
