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Publication : Precise temporal control of the eye regulatory gene Pax6 via enhancer-binding site affinity.

First Author  Rowan S Year  2010
Journal  Genes Dev Volume  24
Issue  10 Pages  980-5
PubMed ID  20413611 Mgi Jnum  J:160146
Mgi Id  MGI:4453504 Doi  10.1101/gad.1890410
Citation  Rowan S, et al. (2010) Precise temporal control of the eye regulatory gene Pax6 via enhancer-binding site affinity. Genes Dev 24(10):980-5
abstractText  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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