The enhancer-blocking suppressor of Hairy-wing zinc finger protein of Drosophila melanogaster alters DNA structure

Insertion of the gypsy retrotransposon of Drosophila melanogaster into a gene control region can repress gene expression. The zinc finger protein (SUHW) encoded by the suppressor of Hairy-wing [su(Hw)] gene binds to gypsy and prevents gene enhancers from activating transcription. SUHW blocks an enhancer only when positioned between the enhancer and promoter. Although position dependent, SUHW enhancer blocking is distance independent. These properties indicate that SUHW does not interact with the transcription activator proteins that bind to enhancers. To explore if DNA distortions are involved in enhancer blocking, the ability of SUHW to alter DNA structure was examined in gel mobility assays. Indeed, SUHW induces an unusual change in the structure of the binding-site DNA. The change is not a directed DNA bend but correlates with loss of sequence-directed bends in the unbound DNA. The DNA distortion requires a SUHW protein domain not required for DNA binding, and mutant proteins that fail to alter DNA structure also fail to eliminate the sequence-directed bends. These results suggest that SUHW increases DNA flexibility. The DNA distortion is not sufficient to block enhancers, and therefore it is suggested that increased DNA flexibility may help SUHW interact and interfere with proteins that support long-distance enhancer-promoter interactions.