Selective repression of transcriptional activators at a distance by the Drosophila Krüppel protein

The Krüppel (Kr) protein, bound at kilobase distances from the start site of transcription, represses transcription by RNA polymerase II in mammalian cells. Repression is monotonically dependent on the dose of Kr protein and the presence of Kr binding site(s) on the DNA. These data suggest an inhibitory protein-protein interaction between the Kr protein and proximal transcription factors. Repression by Kr depends on the specific activator protein driving transcription. In particular, Kr protein selectively represses transcription mediated by the Sp1 glutamine-rich activation domain, tethered to the promoter by a GAL4 DNA-binding domain, but does not repress transcription stimulated by the acidic GAL4 activator. We believe this represents repression by a quenching interaction between DNA-bound Kr protein and the activation region of Sp1, rather than competition between Sp1 and Kr for a limiting transcriptional component. Selective, context-related repression affords an added layer of combinatorial control of gene expression by sequence-specific transcription factors.