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

David S. Parker, Michael A. White, Andrea I. Ramos, Barak A. Cohen, Scott Barolo*

*To whom correspondence should be addressed. E-mail: sbarolo{at}umich.edu

This PDF file includes:

• Text 1. Modeling different biophysical mechanisms.
• Text 2. Parameter sensitivity analysis of repressor cooperativity and differential affinity models.
• Text 3. Testing model fits.
• Methods
• Fig. S1. Annotated sequences of enhancer constructs.
• Fig. S2. Relative in vitro binding affinities of Ci binding sites regulating ptc and dpp.
• Fig. S3. Twelve-species alignments of Ci binding sites.
• Fig. S4. Improving the affinity of Ci sites in the dppD enhancer causes misinterpretation of Hh gradients and lethal developmental defects.
• Fig. S5. Overgrowth and patterning defects in imaginal discs of dppD-Ci^ptc>dpp transgenic larvae.
• Fig. S6. Best fits of four general classes of biophysical models to high-affinity (3xCi^ptc) and low-affinity (3xCi^wt) data.
• Fig. S7. Best-fit equal-affinity models of individual cooperative mechanisms.
• Fig. S8. Prediction of single high-affinity site expression by repressor cooperativity and differential affinity models trained on new or old data.
• Fig. S9. Repressor cooperativity and differential affinity model sensitivity to parameter changes.
• Fig. S10. Repressor and activator occupancy of high- and low-affinity enhancers.
• Table S1. Sequences of EMSA oligonucleotides.
• Table S2. Parameters included in the model.
• Table S3. Best-fit parameter values of four general models.
• Table S4. Parameters for repressor cooperativity and differential affinity models.
• References

[Download PDF]

Technical Details

Format: Adobe Acrobat PDF

Size: 682 KB

© 2011 American Association for the Advancement of Science