Rowan, SheldonSiggers, TrevorLachke, Salil A.Yue, YingziBulyk, Martha L.Maas, Richard L.2019-10-052010Rowan, S., T. Siggers, S. A. Lachke, Y. Yue, M. L. Bulyk, and R. L. Maas. 2010. “Precise Temporal Control of the Eye Regulatory Gene Pax6 via Enhancer-Binding Site Affinity.” Genes & Development 24 (10): 980–85. https://doi.org/10.1101/gad.1890410.0890-93691549-5477http://nrs.harvard.edu/urn-3:HUL.InstRepos:41482936How transcription factors interpret the cis-regulatory logic encoded within enhancers to mediate quantitative changes in spatiotemporally restricted expression patterns during animal development is not well understood. Pax6 is a dosage-sensitive gene essential for eye development. Here, we identify the Prep1 (pKnox1) transcription factor as a critical dose-dependent upstream regulator of Pax6 expression during lens formation. We show that Prep1 activates the Pax6 lens enhancer by binding to two phylogenetically conserved lower-affinity DNA-binding sites. Finally, we describe a mechanism whereby Pax6 levels are determined by transcriptional synergy of Prep1 bound to the two sites, while timing of enhancer activation is determined by binding site affinity.en-USJournal Article2019-10-0510.1101/gad.1890410