Abstract
Hunchback is a bifunctional transcription factor that can activate and repress gene expression in Drosophila development. We investigated the regulatory DNA sequence features that control Hunchback function by perturbing enhancers for one of its target genes, even-skipped (eve). While Hunchback directly represses the eve stripe 3+7 enhancer, we found that in the eve stripe 2+7 enhancer, Hunchback repression is prevented by nearby sequences—this phenomenon is called counter-repression. We also found evidence that Caudal binding sites are responsible for counter-repression, and that this interaction may be a conserved feature of eve stripe 2 enhancers. Our results alter the textbook view of eve stripe 2 regulation wherein Hb is described as a direct activator. Instead, to generate stripe 2, Hunchback repression must be counteracted. We discuss how counter-repression may influence eve stripe 2 regulation and evolution.
Highlights
Bifunctional transcription factors (TFs) that can activate or repress their target genes are critical in animal development [1,2] and are associated with human disease [3,4]
We removed predicted Hb binding sites from eve3+7 using the most current position weight matrices (PWMs) available; PWMs allow us to predict TF binding at a variety of different stringencies
We used the same method to test for a correlation in Hb and Bcd enrichment scores for eve2 and eve3+7 orthologs, but we observed no significant correlation in either case (S8 Fig). These results suggest that counter-repression of Hb by Cad is a conserved feature of eve stripe 2 enhancers, we cannot rule out the possibility that a similar interaction occurs in eve3+7
Summary
Bifunctional transcription factors (TFs) that can activate or repress their target genes are critical in animal development [1,2] and are associated with human disease [3,4]. The function of these TFs can depend on the context of the enhancer sequences they bind [5,6,7,8,9]. Its bifunctional role in regulating the pair-rule gene even-skipped (eve) has been well-studied. Qualitative measurements of mutated versions of the eve stripe 3+7 enhancer (eve3+7) driving reporter gene expression suggested that Hb repression of eve3+7 is direct [15,17,25,26]
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