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EGF 受体信号梯度的转录解读。

Transcriptional interpretation of the EGF receptor signaling gradient.

机构信息

Institute for Biology I, Faculty of Biology, Albert-Ludwigs-University of Freiburg, 79104 Freiburg, Germany.

出版信息

Proc Natl Acad Sci U S A. 2012 Jan 31;109(5):1572-7. doi: 10.1073/pnas.1115190109. Epub 2012 Jan 17.

Abstract

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.

摘要

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,EGFR 的激活模式形成了滤泡上皮的梯度。该组织中 EGFR 的多个转录靶标已被鉴定,但它们的调节元件基本未知。我们报告了果蝇卵子发生中 EGFR 信号的两个重要靶标 broad (br) 和 pipe (pip) 的调节元件。br 以一种复杂的模式表达,预示着呼吸卵壳附属物的形成。我们发现,这种模式是由两个调节元件的动态活动产生的,这两个调节元件对参与 EGFR 介导的基因表达的转录因子 Pointed、Capicua 和 Mirror 表现出不同的反应。其中一个元件的活性模式与受 EGFR 抑制并对胚胎背腹极性建立至关重要的基因 pip 相似。我们证明这种表达的相似性取决于一个共同的序列基序,该基序在体外与 Mirror 结合,并且对于体内转录抑制是必需的。

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