ArticleScience signaling2011
The cis-regulatory logic of Hedgehog gradient responses: key roles for gli binding affinity, competition, and cooperativity.
Article in Science signaling, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 108 citations in OpenAlex.
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- Patterning of theFrontiers in cell and developmental biology · 2023Review
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- Concentration-dependent transcriptional switching through a collective action of cis-elements.Science advances · 2022Article
- Engrailed, Suppressor of fused and Roadkill modulate the Drosophila GLI transcription factor Cubitus interruptus at multiple levels.Development (Cambridge, England) · 2022Article
- GLI transcriptional repression is inert prior to Hedgehog pathway activation.Nature communications · 2022Article
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- Gli3 utilizes Hand2 to synergistically regulate tissue-specific transcriptional networks.eLife · 2020Article
- Transcriptional Enhancers inGenetics · 2020Review
- Expression of E93 provides an instructive cue to control dynamic enhancer activity and chromatin accessibility during development.Development (Cambridge, England) · 2020Article
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- Multimodal transcriptional control of pattern formation in embryonic development.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Analysis of the transcriptional logic governing differential spatial expression in Hh target genes.PloS one · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Gradients of diffusible signaling proteins control precise spatial patterns of gene expression in the developing embryo. Here, we use quantitative expression measurements and thermodynamic modeling to uncover the cis-regulatory logic underlying spatially restricted gene expression in a Hedgehog (Hh) gradient in Drosophila. When Hh signaling is low, the Hh effector Gli, known as Cubitus interruptus (Ci) in Drosophila, acts as a transcriptional repressor; when Hh signaling is high, Gli acts as a transcriptional activator. Counterintuitively and in contrast to previous models of Gli-regulated gene expression, we found that low-affinity binding sites for Ci were required for proper spatial expression of the Hh target gene decapentaplegic (dpp) in regions of low Hh signal. Three low-affinity Ci sites enabled expression of dpp in response to low signal; increasing the affinity of these sites restricted dpp expression to regions of maximal signaling. A model incorporating cooperative repression by Ci correctly predicted the in vivo expression of a reporter gene controlled by a single Ci site. Our work clarifies how transcriptional activators and repressors, competing for common binding sites, can transmit positional information to the genome. It also provides an explanation for the widespread presence of conserved, nonconsensus Gli binding sites in Hh target genes.
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