Deadpan contributes to the robustness of the notch response.
Deadpan contributes to the robustness of the notch response.
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DOI：
10.1371/journal.pone.0075632
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Bray SJ
中科院分区：
文献类型：
--
作者：
Babaoğlan AB;Housden BE;Furriols M;Bray SJ
Notch信号调节许多基本事件，包括侧抑制和边界形成，以在发育中的组织中产生非常可重复性的模式。它的靶标包括bHLH毛发和Split[E(SPL)]家族的增强子基因，这些基因对许多这些发育决定都有贡献。在果蝇中，这个家族的成员之一，死板(Dpn)，最初被发现在促进神经发育方面具有独立于Notch的功能。利用全基因组染色质免疫沉淀，我们在DPN中鉴定了几个Notch反应增强子，证明了它在包括果蝇翅膀和眼睛在内的一系列环境中受到Notch的直接调节。DPN的表达在很大程度上与几个E(SPL)基因的表达重叠，并且联合敲除导致比单独的任何一个更严重的表型。此外，DPN有助于在翅膀背侧-腹侧(D/V)边界建立CUT表达；如果没有它，CUT表达被推迟。此外，DPN的过度表达抑制了E(SPL)基因增强子的表达，但反之亦然，这表明DPN参与了一种反馈机制，限制了Notch激活后E(SPL)基因的表达。因此，dpn和E(Spl)的联合作用似乎提供了一种机制，即通过靶点之间的反馈，给予Notch活动最初的快速输出，使其变得自限。
Notch signaling regulates many fundamental events including lateral inhibition and boundary formation to generate very reproducible patterns in developing tissues. Its targets include genes of the bHLH hairy and Enhancer of split [E(spl)] family, which contribute to many of these developmental decisions. One member of this family in Drosophila, deadpan (dpn), was originally found to have functions independent of Notch in promoting neural development. Employing genome-wide chromatin-immunoprecipitation we have identified several Notch responsive enhancers in dpn, demonstrating its direct regulation by Notch in a range of contexts including the Drosophila wing and eye. dpn expression largely overlaps that of several E(spl) genes and the combined knock-down leads to more severe phenotypes than either alone. In addition, Dpn contributes to the establishment of Cut expression at the wing dorsal-ventral (D/V) boundary; in its absence Cut expression is delayed. Furthermore, over-expression of Dpn inhibits expression from E(spl) gene enhancers, but not vice versa, suggesting that dpn contributes to a feed-back mechanism that limits E(spl) gene expression following Notch activation. Thus the combined actions of dpn and E(spl) appear to provide a mechanism that confers an initial rapid output from Notch activity which becomes self-limited via feedback between the targets.
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