A LEUCINE-ZIPPER DOMAIN OF THE SUPPRESSOR OF HAIRY-WING PROTEIN MEDIATES ITS REPRESSIVE EFFECT ON ENHANCER FUNCTION

The suppressor of Hairy-wing [su(Hw)] protein mediates the mutagenic e ffect of the gypsy retrotransposon by repressing the function of trans criptional enhancers controlling the expression of the mutant gene. A structural and functional analysis of su(Hw) was carried out to identi fy domains of the protein responsible for its negative effect on enhan cer action. Sequence comparison among the su(Hw) proteins from three d ifferent species allows the identification of evolutionarily conserved domains with possible functional significance. An acidic domain locat ed in the carboxy-terminal end of the Drosophila melanogaster protein is not present in su(Hw) from other species, suggesting a nonessential role for this part of the protein. A second acidic domain located in the amino-terminal region of su(Hw) is present in all species analyzed . This domain is dispensable in the D. melanogaster protein when the c arboxy-terminal acidic domain is present, but the protein is nonfuncti onal when both regions are simultaneously deleted. Mutations in the zi nc fingers result in su(Hw) protein unable to interact with DNA in viv o, indicating a functional role for this region of the protein in DNA binding. Finally, a region of su(Hw) homologous to the leucine zipper motif is necessary for the negative effect of this protein on enhancer function, suggesting that su(Hw) might exert this effect by interacti ng, directly or indirectly, with transcription factors bound to these enhancers.