Transcriptional interpretation of the EGF receptor signaling gradient
Transcriptional interpretation of the EGF receptor signaling gradient
复制标题
DOI：
10.1073/pnas.1115190109
复制
发表时间：
2012-01-31
影响因子：
11.1
通讯作者：
Pyrowolakis, George
中科院分区：
文献类型：
--
作者：
Fuchs, Alisa;Cheung, Lily S.;Pyrowolakis, George
表皮生长因子受体（EGFR）控制着广泛的发育事件，从昆虫的体轴特化到人类的心脏发育。在果蝇卵子发生过程中，表皮生长因子受体激活的梯度图案滤泡上皮。EGFR在该组织中的多个转录靶点已被确定，但其调控元件基本上是未知的。我们报告广泛的（br）和管道（pip），在果蝇卵子发生的EGFR信号的两个重要目标的调节元件。br以复杂的模式表达，预示着呼吸蛋壳附属物的形成。我们发现，这种模式是由两个调控元件的动态活动产生的，这两个调控元件对参与EGFR介导的基因表达的Pointed、Capicua和Mirror转录因子表现出不同的反应。这些元素之一是活跃的模式类似于pip，一个基因抑制EGFR和建立胚胎的背腹极性必不可少的。我们证明，这种相似性的表达依赖于一个共同的序列基序，结合镜像在体外，是必不可少的体内转录抑制。
Epidermal growth factor receptor (EGFR) controls a wide range of developmental events, from body axes specification in insects to cardiac development in humans. During Drosophila oogenesis, a gradient of EGFR activation patterns the follicular epithelium. Multiple transcriptional targets of EGFR in this tissue have been identified, but their regulatory elements are essentially unknown. We report the regulatory elements of broad (br) and pipe (pip), two important targets of EGFR signaling in Drosophila oogenesis. br is expressed in a complex pattern that prefigures the formation of respiratory eggshell appendages. We found that this pattern is generated by dynamic activities of two regulatory elements, which display different responses to Pointed, Capicua, and Mirror, transcription factors involved in the EGFR-mediated gene expression. One of these elements is active in a pattern similar to pip, a gene repressed by EGFR and essential for establishing the dorsoventral polarity of the embryo. We demonstrate that this similarity of expression depends on a common sequence motif that binds Mirror in vitro and is essential for transcriptional repression in vivo.