Drosophila MBF1 is a co-activator for Tracheae Defective and contributes to the formation of tracheal and nervous systems
Drosophila MBF1 is a co-activator for Tracheae Defective and contributes to the formation of tracheal and nervous systems
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DOI：
10.1242/dev.00297
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发表时间：
2003-02-01
期刊：
影响因子：
4.6
通讯作者：
Hirose, S
中科院分区：
文献类型：
--
作者：
Liu, QX;Jindra, M;Hirose, S
在基因激活过程中，转录因子与顺式作用 DNA 序列结合的效果通过共激活剂传递给 RNA 聚合酶。尽管共激活因子有助于提高转录效率，但人们对它们的发育作用知之甚少。我们使用果蝇对多细胞生物体中一种进化上保守但独特的共激活因子多蛋白桥接因子 1 (MBF1) 进行分子和遗传解剖。通过免疫沉淀，发现MBF1形成三元复合物，包括MBF1、TATA结合蛋白(TBP)和bZIP蛋白气管缺陷(TDF)/Apontic。我们分离出一种缺乏 mbf1 基因的果蝇突变体，其中未检测到 TBP 和 TDF 之间的稳定关联，并且 TDF 依赖性报告基因的转录减少了 80%。虽然 mbf1 的无效突变体是可行的，但 tdf 在 mbf1 缺陷的背景下变得单倍体不足，导致气管和中枢神经系统严重损伤，类似于 tdf 功能完全丧失造成的损伤。这些数据证明了 MBF1 在气管和中枢神经系统发育中的关键作用。
During gene activation, the effect of binding of transcription factors to cis-acting DNA sequences is transmitted to RNA polymerase by means of co-activators. Although co-activators contribute to the efficiency of transcription, their developmental roles are poorly understood. We used Drosophila to conduct molecular and genetic dissection of an evolutionarily conserved but unique co-activator, Multiprotein Bridging Factor 1 (MBF1), in a multicellular organism. Through immunoprecipitation, MBF1 was found to form a ternary complex including MBF1, TATA-binding protein (TBP) and the bZIP protein Tracheae Defective (TDF)/Apontic. We have isolated a Drosophila mutant that lacks the mbf1 gene in which no stable association between TBP and TDF is detectable, and transcription of a TDF-dependent reporter gene is reduced by 80%. Although the null mutants of mbf1 are viable, tdf becomes haploinsufficient in mbf1-deficient background, causing severe lesions in tracheae and the central nervous system, similar to those resulting from a complete loss of tdf function. These data demonstrate a crucial role of MBF1 in the development of tracheae and central nervous system.