A direct contact between the dorsal rel homology domain and Twist may mediate transcriptional synergy.
The establishment of mesoderm and neuroectoderm in the early Drosophila embryo relies on interactions between the Dorsal morphogen and basic-helix-loop-helix (bHLH) activators. Here we show that Dorsal and the bHLH activator Twist synergistically activate transcription in cell culture and in vitro from a promoter containing binding sites for both factors. Somewhat surprisingly, a region of Twist outside the conserved bHLH domain is required for the synergy. In Dorsal, the rel homology domain appears to be sufficient for synergy. Protein-protein interaction assays show that Twist and Dorsal bind to one another in vitro. However, this interaction does not appear to be of sufficient strength to yield cooperative binding to DNA. Nonetheless, the regions of Twist and Dorsal required for the binding interaction are also required for synergistic transcriptional activation.
Shirokawa
J M
JM
Department of Chemistry and Biochemistry, University of California, Los Angeles 90095-1569, USA.
Courey
A J
AJ
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002474:Cell-Free System; D002478:Cells, Cultured; D017124:Conserved Sequence; D004330:Drosophila; D029721:Drosophila Proteins; D006367:HeLa Cells; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D009857:Oncogenes / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D051879:Twist-Related Protein 1
D029721:Drosophila Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C103173:TWIST1 protein, human; D014157:Transcription Factors; C497753:Twi protein, Drosophila; D051879:Twist-Related Protein 1; C062236:dl protein, Drosophila