Jun S, Desplan C
Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
Development. 1996 Sep;122(9):2639-50. doi: 10.1242/dev.122.9.2639.
The Pax proteins are a family of transcriptional regulators involved in many developmental processes in all higher eukaryotes. They are characterized by the presence of a paired domain (PD), a bipartite DNA binding domain composed of two helix-turn-helix (HTH) motifs,the PAI and RED domains. The PD is also often associated with a homeodomain (HD) which is itself able to form homo- and hetero-dimers on DNA. Many of these proteins therefore contain three HTH motifs each able to recognize DNA. However, all PDs recognize highly related DNA sequences, and most HDs also recognize almost identical sites. We show here that different Pax proteins use multiple combinations of their HTHs to recognize several types of target sites. For instance, the Drosophila Paired protein can bind, in vitro, exclusively through its PAI domain, or through a dimer of its HD, or through cooperative interaction between PAI domain and HD. However, prd function in vivo requires the synergistic action of both the PAI domain and the HD. Pax proteins with only a PD appear to require both PAI and RED domains, while a Pax-6 isoform and a new Pax protein, Lune, may rely on the RED domain and HD. We propose a model by which Pax proteins recognize different target genes in vivo through various combinations of their DNA binding domains, thus expanding their recognition repertoire.
Pax蛋白是一类转录调节因子，参与所有高等真核生物的许多发育过程。它们的特征是存在一个配对结构域（PD），这是一个由两个螺旋-转角-螺旋（HTH）基序组成的二分DNA结合结构域，即PAI和RED结构域。PD通常还与一个同源异型结构域（HD）相关联，该结构域本身能够在DNA上形成同源二聚体和异源二聚体。因此，许多这类蛋白质各自包含三个能够识别DNA的HTH基序。然而，所有的PD都识别高度相关的DNA序列，并且大多数HD也识别几乎相同的位点。我们在此表明，不同的Pax蛋白利用其HTH的多种组合来识别几种类型的靶位点。例如，果蝇的成对蛋白在体外可以仅通过其PAI结构域结合，或通过其HD的二聚体结合，或通过PAI结构域与HD之间的协同相互作用结合。然而，成对蛋白在体内的功能需要PAI结构域和HD的协同作用。仅具有PD的Pax蛋白似乎需要PAI和RED结构域，而一种Pax-6异构体和一种新的Pax蛋白Lune可能依赖于RED结构域和HD。我们提出了一个模型，通过该模型Pax蛋白在体内通过其DNA结合结构域的各种组合识别不同的靶基因，从而扩展其识别范围。
