Gause Maria, Eissenberg Joel C, Macrae Amy F, Dorsett Maia, Misulovin Ziva, Dorsett Dale
Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1402 South Grand Boulevard, Saint Louis, MO 63104, USA.
Mol Cell Biol. 2006 Mar;26(6):2347-59. doi: 10.1128/MCB.26.6.2347-2359.2006.
The Notch receptor controls development by activating transcription of specific target genes in response to extracellular signals. The factors that control assembly of the Notch activator complex on target genes and its ability to activate transcription are not fully known. Here we show, through genetic and molecular analysis, that the Drosophila Nipped-A protein is required for activity of Notch and its coactivator protein, mastermind, during wing development. Nipped-A and mastermind also colocalize extensively on salivary gland polytene chromosomes, and reducing Nipped-A activity decreases mastermind binding. Nipped-A is the fly homologue of the yeast Tra1 and human TRRAP proteins and is a key component of both the SAGA and Tip60 (NuA4) chromatin-modifying complexes. We find that, like Nipped-A, the Ada2b component of SAGA and the domino subunit of Tip60 are also required for mastermind function during wing development. Based on these results, we propose that Nipped-A, through the action of the SAGA and Tip60 complexes, facilitates assembly of the Notch activator complex and target gene transcription.
Notch受体通过响应细胞外信号激活特定靶基因的转录来控制发育。控制Notch激活复合物在靶基因上的组装及其激活转录能力的因素尚不完全清楚。在这里，我们通过遗传和分子分析表明，果蝇Nipped-A蛋白在翅膀发育过程中是Notch及其共激活蛋白mastermind活性所必需的。Nipped-A和mastermind也在唾液腺多线染色体上广泛共定位，降低Nipped-A活性会减少mastermind的结合。Nipped-A是酵母Tra1和人类TRRAP蛋白的果蝇同源物，是SAGA和Tip60（NuA4）染色质修饰复合物的关键组成部分。我们发现，与Nipped-A一样，SAGA的Ada2b组分和Tip60的domino亚基在翅膀发育过程中也是mastermind功能所必需的。基于这些结果，我们提出，Nipped-A通过SAGA和Tip60复合物的作用，促进Notch激活复合物的组装和靶基因转录。
