Brodu V, Mugat B, Roignant J Y, Lepesant J A, Antoniewski C
Institut Jacques Monod, Laboratoire de Biologie du Développement, CNRS UMR 7592, Université Paris 7 Denis-Diderot, Université Paris 6 P. et M. Curie, 75251 Paris Cedex 05, France.
Mol Cell Biol. 1999 Aug;19(8):5732-42. doi: 10.1128/MCB.19.8.5732.
The EcR/USP nuclear receptor controls Drosophila metamorphosis by activating complex cascades of gene transcription in response to pulses of the steroid hormone ecdysone at the end of larval development. Ecdysone release provides a ubiquitous signal for the activation of the receptor, but a number of its target genes are induced in a tissue- and stage-specific manner. Little is known about the molecular mechanisms involved in this developmental modulation of the EcR/USP-mediated pathway. Fbp1 is a good model of primary ecdysone response gene expressed in the fat body for addressing this question. We show here that the dGATAb factor binds to three target sites flanking an EcR/USP binding site in a 70-bp enhancer that controls the tissue and stage specificity of Fbp1 transcription. We demonstrate that one of these sites and proper expression of dGATAb are required for specific activation of the enhancer in the fat body. In addition, we provide further evidence that EcR/USP plays an essential role as a hormonal timer. Our study provides a striking example of the integration of molecular pathways at the level of a tissue-specific hormone response unit.
EcR/USP核受体通过在幼虫发育末期响应类固醇激素蜕皮激素脉冲激活复杂的基因转录级联反应,从而控制果蝇的变态发育。蜕皮激素的释放为受体激活提供了一个普遍存在的信号,但其许多靶基因是以组织和阶段特异性的方式被诱导的。关于EcR/USP介导途径的这种发育调控所涉及的分子机制,我们知之甚少。Fbp1是在脂肪体中表达的初级蜕皮激素反应基因的一个很好的模型,可用于解决这个问题。我们在此表明,dGATAb因子与一个70bp增强子中EcR/USP结合位点侧翼的三个靶位点结合,该增强子控制Fbp1转录的组织和阶段特异性。我们证明,这些位点之一和dGATAb的正确表达是脂肪体中增强子特异性激活所必需的。此外,我们提供了进一步的证据,证明EcR/USP作为激素定时器发挥着至关重要的作用。我们的研究提供了一个在组织特异性激素反应单元水平上分子途径整合的显著例子。