The ci(D) mutation encodes a chimeric protein whose activity is regulated by wingless signaling

Abstract

The Drosophila cubitus interruptus (ci) gene encodes a sequence-specific DNA-binding protein that regulates transcription of Hedgehog (Hh) target genes. Activity of the Ci protein is posttranslationally regulated by Hh signaling. In animals homozygous for the ci(D) mutation, however, transcription of Hh target genes is regulated by Wingless (Wg) signaling rather than by Hh signaling. We show that ci(D) encodes a chimeric protein composed of the regulatory domain of dTCF/Pangolin (Pan) and the DNA binding domain of Ci. Pan is a Wg-regulated transcription factor that is activated by binding of Armadillo (Arm) to its regulatory domain. Arm is thought to activate Pan by contributing a transactivation domain. We find that a constitutively active form of Arm potentiates activity of a CiD transgene and coimmunoprecipitates with CiD protein. The Wg-responsive activity of CiD could be explained by recruitment of the Arm transactivation function to the promoters of Hh-target genes. We suggest that wild-type Ci also recruits a protein with a transactivation domain as part of its normal mechanism of activation.