Publication: Precise temporal control of the eye regulatory gene Pax6 via enhancer-binding site affinity
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2010
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Cold Spring Harbor Laboratory Press
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Rowan, 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.
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Abstract
How 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.
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