Suppressor of Hairy-wing Su(Hw) is a DNA-binding architectural protein that participates in the organization of insulators and repression of promoters in Drosophila. This protein contains acidic regions at both ends and a central cluster of 12 zinc finger domains, some of which are involved in the specific recognition of the binding site. One of the well-described in vivo function of Su(Hw) is the repression of transcription of neuronal genes in oocytes. Here, we have found that the same Su(Hw) C-terminal region (aa 720-892) is required for insulation as well as for promoter repression. The best characterized partners of Su(Hw), CP190 and Mod(mdg4)-67.2, are not involved in the repression of neuronal genes. Taken together, these results suggest that an unknown protein or protein complex binds to the C-terminal region of Su(Hw) and is responsible for the direct repression activity of Su(Hw).