The cis-Regulatory Logic of Hedgehog Gradient Responses: Key Roles for Gli Binding Affinity, Competition, and Cooperativity

D. S. Parker, M. A. White, A. I. Ramos, B. A. Cohen, S. Barolo
2011 Science Signaling  
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
more » ... ranscriptional 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
doi:10.1126/scisignal.2002077 pmid:21653228 pmcid:PMC3152249 fatcat:c3uinvnprvdnxaxod6zudwbzea