THE PAIRED BOX ENCODES A 2ND DNA-BINDING DOMAIN IN THE PAIRED HOMEO DOMAIN PROTEIN
THE PAIRED BOX ENCODES A 2ND DNA-BINDING DOMAIN IN THE PAIRED HOMEO DOMAIN PROTEIN
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DOI：
10.1101/gad.5.4.594
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发表时间：
1991-04-01
影响因子：
10.5
通讯作者：
DESPLAN, C
中科院分区：
文献类型：
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作者：
TREISMAN, J;HARRIS, E;DESPLAN, C
同源盒编码 DNA 结合同源结构域，是存在于几种果蝇发育基因中的 DNA 序列基序。它已被用来鉴定许多与哺乳动物发育有关的同源基因。 配对盒是另一个保守序列基序，首先在配对 (prd) 和醋栗 (gsb) 果蝇同源结构域基因中发现。 它编码一个 128 个氨基酸的结构域，即配对结构域，此后在其他果蝇和小鼠基因产物中发现了该结构域，与同源结构域相关或不存在。 我们表明，prd 基因的配对盒编码 DNA 结合活性，独立于配对 (Prd) 同源结构域的 DNA 结合活性，并具有不同的序列特异性。 配对结构域的氨基末端区域，包括三个预测的 α 螺旋之一，对于结合是必要且充分的。 我们研究了 Prd 蛋白与偶数跳跃启动子中两个位点的结合，这两个位点由同源结构域和配对结构域结合的重叠序列组成。 我们还表明，Prd 配对盒中的突变（与被认为导致波动骨骼表型的小鼠 Pax-1 基因配对盒中的突变相对应）破坏了 Prd 蛋白与配对结构域特异性位点结合的能力。 这支持了以下观点：波状表型是由于 Pax-1 配对结构域的 DNA 结合活性失活所致。
The homeo box, which encodes the DNA-binding homeo domain, is a DNA sequence motif present in several Drosophila developmental genes; it has been used to identify many homologous genes involved in mammalian development. The paired box is another conserved sequence motif, first identified in the paired (prd) and gooseberry (gsb) Drosophila homeo domain genes. It encodes a 128-amino-acid domain, the paired domain, which has since been found in other fly and mouse gene products, in association with the homeo domain or in its absence. We show that the paired box of the prd gene encodes a DNA-binding activity, independent of the DNA-binding activity of the Paired (Prd) homeo domain and with a different sequence specificity. The amino-terminal region of the paired domain, including one of the three predicted alpha-helices, is necessary and sufficient for binding. We investigate the binding of the Prd protein to two sites in the even-skipped promoter, which are composed of overlapping sequences bound by the homeo domain and by the paired domain. We also show that a mutation in the paired box of Prd, corresponding to the mutation in the paired box of the mouse Pax-1 gene thought to cause the undulated skeletal phenotype, destroys the ability of the Prd protein to bind to the paired domain-specific site. This supports the view that the undulated phenotype results from the inactivation of the DNA-binding activity of the paired domain of Pax-1.