Functional studies of the BTB domain in the Drosophila GAGA and Mod(mdg4) proteins

The BTB/POZ (BTB) domain is an approximately 120 residue sequence that is c onserved at the N-terminus of many proteins in both vertebrates and inverte brates. We found that the protein encoded by a lethal allele of the Drosoph ila modifier of mdg4 [mod(mdg4)] gene has two mutated residues in its BTB d omain. The identities of the residues at the positions of these mutations a re highly conserved in the BTB domain family of proteins, and when the corr esponding mutations were engineered into the BTB domain-containing GAGA pro tein, the activity of GAGA as a transcription activator in a transient tran sfection assay was severely reduced. The functional equivalence of the BTB domains was established by showing that the BTB domain of the mod(mdg4) pro tein can effectively substitute for that of GAGA.