Drosophila MBF1 is a co-activator for Tracheae Defective and contributes to the formation of tracheal and nervous systems.
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.
Liu
Qing-Xin
QX
Department of Developmental Genetics, National Institute of Genetics, Graduate University for Advanced Studies, Mishima, Shizuoka-ken 411-8540, Japan.
Jindra
Marek
M
Ueda
Hitoshi
H
Hiromi
Yasushi
Y
Hirose
Susumu
S
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D008969:Molecular Sequence Data; D009420:Nervous System / Q000196:embryology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D035181:TATA-Box Binding Protein / Q000235:genetics / Q000378:metabolism; D014132:Trachea / Q000196:embryology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C491465:MBF1 protein, Drosophila; D009687:Nuclear Proteins; D035181:TATA-Box Binding Protein; D015534:Trans-Activators; D014157:Transcription Factors; C108529:apt protein, Drosophila