Ci binding affinity mediates universal and tissue-specific expression patterns in response to Hedgehog signaling
Sipahi, Levent H.
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A fundamental problem in developmental biology is the understanding of how a limited number of signal transduction pathways can yield vast, spatially diverse, patterns of expression. This phenomenon is generally explained by the combinatorial control model, which predicts that any combination of signal pathway-associated transcription factors (TFs) alone are insufficient to generate a transcriptional response (activator insufficiency), but require the additional input of cell-type-specific TFs (cooperative activation). Differential responses among target genes to a single signaling pathway have been demonstrated in the past to be due to TF binding affinity. However each of these has utilized a morphogen gradient to mediate differential expression within a single tissue. Here, we provide evidence for TF binding affinity being a regulatory tool for tissue specific vs. universal response to a signaling pathway among multiple tissues. In this study, we examined the responsiveness to Hedgehog signaling of Cubitus interruptus (Ci) binding sites of different binding affinity in the context and independent of the ptc enhancer using Enhancer-LacZ reporter constructs in transgenic fly lines. Our results suggest that I) the ptc enhancer requires high affinity Ci binding sites in order to be universally responsive to Hedgehog signaling and 2) a single high affinity Ci binding site is sufficient to mediate universal response to Hedgehog signaling. These data reveal an added complexity to the combinatorial control model of transcriptional regulation and provide further characterization of the ptc enhancer's response to Hedgehog signaling.