通过增强子结合位点亲和力精确控制眼部调节基因 Pax6 的时间。
Precise temporal control of the eye regulatory gene Pax6 via enhancer-binding site affinity.
机构信息
Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
出版信息
Genes Dev. 2010 May 15;24(10):980-5. doi: 10.1101/gad.1890410. Epub 2010 Apr 22.
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.
摘要
在动物发育过程中，转录因子如何解读增强子中编码的顺式调控逻辑，从而介导时空受限表达模式的定量变化，目前还不太清楚。Pax6 是一个剂量敏感基因，对眼睛发育至关重要。在这里，我们确定了 Prep1（pKnox1）转录因子是晶状体形成过程中 Pax6 表达的关键剂量依赖性上游调节剂。我们表明，Prep1 通过结合两个系统发育上保守的低亲和力 DNA 结合位点来激活 Pax6 晶状体增强子。最后，我们描述了一种机制，其中 Pax6 的水平由结合到两个位点的 Prep1 的转录协同作用决定，而增强子的激活时间则由结合位点的亲和力决定。
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