An HMG-like protein that can switch a transcriptional activator to a repressor

ONE protein can activate some genes and repress others in the same cell 1 . The Drosophila protein Dorsal 2 (which, like the human protein NF-κB 3 , is a member of the Rel family of transcriptional activators) activates the twist gene and represses the zen gene in the ventral region of early embryos 4,5 . Here we describe a Drosophila HMG1 protein, called DSP1 (dorsal switch protein), that converts Dorsal and NF-κB from transcriptional activators to repressers. This effect requires a sequence termed a negative regulatory ele-ment (NRE), found adjacent to Dorsal-binding sites in the zen promoter and adjacent to the NF-κB-binding site in the human interferon-β (IFN-β) enhancer 6–8 . Previous studies have shown that another type of HMG protein, HMG I(Y), can stimulate NF-κB activity 9 . Thus, the HMG-like proteins DSP1 and HMG I(Y) can determine whether a specific regulator functions as an activator or a repressor of transcription.