Ectopic expression of wild-type or a dominant-negative mutant of transcription factor NTF-1 disrupts normal Drosophila development.
The Drosophila melanogaster tissue-specific transcription factor NTF-1 was originally identified in vitro as a protein that could bind to and activate transcription from the Dopa decarboxylase (Ddc) gene. A structure-function analysis of NTF-1 led to the identification of a discrete amino-terminal activation domain. Here, we report that an NTF-1 mutant lacking the activation domain acts as a trans-dominant inhibitor of NTF-1 activation in tissue culture cells by forming inactive heterodimers with the full-length protein. Ectopically expressing this dominant-negative protein or the full-length protein in developing Drosophila embryos leads to dire developmental consequences. Overexpressing the trans-dominant NTF-1 leads to lethality, while overexpressing full-length NTF-1 results in both lethality and morphogenetic defects. Our results suggest that both the activity and the regulation of NTF-1 are critical for viability and proper development of the fly.
Attardi
L D
LD
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Von Seggern
D
D
Tjian
R
R
D000818:Animals; D030801:Animals, Genetically Modified; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology*; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology*; D015870:Gene Expression; D005799:Genes, Dominant; D066298:In Vitro Techniques; D007814:Larva; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000502:physiology*
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C062330:grh protein, Drosophila