Ci binding affinity mediates universal and tissue-specific expression patterns in response to Hedgehog signaling
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Authors
Sipahi, Levent H.
Issue Date
2008
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
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.
Description
v, 40 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.