THE PAS DOMAIN CONFERS TARGET GENE SPECIFICITY OF DROSOPHILA BHLH PASPROTEINS/

Trachealess (Trh) and Single-minded (Sim) are highly similar Drosophil a bHLH/PAS transcription factors. They activate nonoverlapping target genes and induce diverse cell fates. A single Drosophila gene encoding a bHLH/PAS protein homologous to the vertebrate ARNT protein was isol ated and may serve as a partner for both Trh and Sim. We show that Trh and Sim complexes recognize similar DNA-binding sites in the embryo. To examine the basis for their distinct target gene specificity, the a ctivity of Trh-Sim chimeric proteins was monitored in embryos. Replace ment of the Trh PAS domain by the analogous region of Sim was sufficie nt to convert it into a functional Sim protein. The PAS domain thus me diates all the features conferring specificity and the distinct recogn ition of target genes. The normal expression pattern of additional pro teins essential for the activity of the Trh or Sim complexes can be in ferred from the induction pattern of target genes and binding-site rep orters, triggered by ubiquitous expression of Trh or Sim. We postulate that the capacity of bHLH/PAS heterodimers to associate, through the PAS domain, with additional distinct proteins that bind target-gene DN A, is essential to confer specificity.