Liu Qing-Xin, Jindra Marek, Ueda Hitoshi, Hiromi Yasushi, Hirose Susumu
Department of Developmental Genetics, National Institute of Genetics, Graduate University for Advanced Studies, Mishima, Shizuoka-ken 411-8540, Japan.
Development. 2003 Feb;130(4):719-28. doi: 10.1242/dev.00297.
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.
在基因激活过程中，转录因子与顺式作用DNA序列结合的效应通过共激活因子传递给RNA聚合酶。尽管共激活因子有助于提高转录效率，但其在发育中的作用却知之甚少。我们利用果蝇对多细胞生物中一种进化上保守但独特的共激活因子——多蛋白桥联因子1（MBF1）进行了分子和遗传学剖析。通过免疫沉淀发现，MBF1能形成一个三元复合物，其中包括MBF1、TATA结合蛋白（TBP）和bZIP蛋白气管缺陷（TDF）/无触角（Apontic）。我们分离出了一个缺乏mbf1基因的果蝇突变体，在该突变体中检测不到TBP与TDF之间的稳定结合，并且一个依赖TDF的报告基因的转录减少了80%。尽管mbf1的缺失突变体是可存活的，但在mbf1缺陷背景下tdf变得半合子不足，导致气管和中枢神经系统出现严重病变，类似于tdf功能完全丧失所导致的病变。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。
