S. Rowan, T. Siggers, S. A. Lachke, Y. Yue, M. L. Bulyk and R. L. Maas
Year:
2010
Journal:
Genes Dev
Volume:
24
Pages:
980-5
Title:
Precise temporal control of the eye regulatory gene Pax6 via enhancer-binding site affinity
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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