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首页> 外文期刊>Molecular and Cellular Biology >A complex array of positive and negative elements regulates the chicken alpha A-crystallin gene: involvement of Pax-6, USF, CREB and/or CREM, and AP-1 proteins.
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A complex array of positive and negative elements regulates the chicken alpha A-crystallin gene: involvement of Pax-6, USF, CREB and/or CREM, and AP-1 proteins.

机译:正负元素的复杂阵列调节鸡的αA-晶状体蛋白基因:Pax-6,USF,CREB和/或CREM以及AP-1蛋白的参与。

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The abundance of crystallins (> 80% of the soluble protein) in the ocular lens provides advantageous markers for selective gene expression during cellular differentiation. Here we show by functional and protein-DNA binding experiments that the chicken alpha A-crystallin gene is regulated by at least five control elements located at sites A (-148 to -139), B (-138 to -132), C (-128 to -101), D (-102 to -93), and E (-56 to -41). Factors interacting with these sites were characterized immunologically and by gel mobility shift experiments. The results are interpreted with the following model. Site A binds USF and is part of a composite element with site B. Site B binds CREB and/or CREM to enhance expression in the lens and binds an AP-1 complex including CREB, Fra2 and/or JunD which interacts with USF on site A to repress expression in fibroblasts. Sites C and E (which is conserved across species) bind Pax-6 in the lens to stimulate alpha A-crystallin promoter activity. These experiments provide the first direct data that Pax-6 contributes to the lens-specific expression of a crystallin gene. Site D (-104 to -93) binds USF and is a negative element. Thus, the data indicate that USF, CREB and/or CREM (or AP-1 factors), and Pax-6 bind a complex array of positive and negative cis-acting elements of the chicken alpha A-crystallin gene to control high expression in the lens and repression in fibroblasts.
机译:晶状体中大量的晶状蛋白(> 80%的可溶性蛋白)为细胞分化过程中的选择性基因表达提供了有利的标记。在这里,我们通过功能和蛋白质-DNA结合实验表明,鸡αA-晶状体蛋白基因受位于位置A(-148至-139),B(-138至-132),C( -128至-101),D(-102至-93)和E(-56至-41)。与这些位点相互作用的因素通过免疫学和凝胶迁移率迁移实验进行了表征。用以下模型解释结果。部位A结合USF,是与部位B的复合元件的一部分。部位B结合CREB和/或CREM以增强晶状体中的表达,并结合AP-1复合物,包括CREB,Fra2和/或与USF在现场相互作用的JunD抑制成纤维细胞中的表达。位点C和E(在整个物种中是保守的)结合晶状体中的Pax-6,以刺激αA-晶状体蛋白启动子活性。这些实验提供了第一个直接数据,即Pax-6有助于crystallin基因的晶状体特异性表达。站点D(-104至-93)与USF绑定且为负数。因此,数据表明USF,CREB和/或CREM(或AP-1因子)和Pax-6结合了鸡αA-晶状体蛋白基因正,负顺式作用元件的复杂阵列,以控制鸡胚A-crystallin基因的高表达。晶状体和成纤维细胞的抑制。

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