A differential response element for the homeotics at the Antennapedia P1 promoter of Drosophila.

Homeotic genes encode DNA-binding transcription factors that specify the identity of a segment or segments in particular body regions of Drosophila. The developmental specificity of these proteins results from their differential regulation of various target genes. This specificity could be achieved by use of different regulatory elements by the homeoproteins or by use of the same elements in different ways. The Ultrabithorax (UBX), abdominal-A (ABD-A), and Antennapedia (ANTP) homeoproteins differentially regulate the Antennapedia P1 promoter in a cell culture cotransfection assay: UBX and ABD-A repress, whereas ANTP activates P1. Either of two regions of P1 can confer this pattern of differential regulation. One of the regions lies downstream and contains homeoprotein-binding sites flanking a 37-bp region called BetBS. ANTP protein activates transcription through the binding sites, whereas UBX and ABD-A both activate transcription through BetBS and use the flanking binding sites to prevent this effect. Thus, homeoproteins can use the same regulatory element but in very different ways. Chimeric UBX-ANTP proteins and UBX deletion derivatives demonstrate that functional specificity in P1 regulation is dictated mainly by sequences outside the homeodomain, with important determinants in the N-terminal region of the proteins. IMAGES:

同源异形基因（Homeotic genes）编码DNA结合转录因子（DNA-binding transcription factors），可特化果蝇（Drosophila）特定躯体区域内一个或多个体节的发育身份。这类蛋白质的发育特异性源于其对不同靶基因的差异化调控。该特异性可通过两种路径实现：同源异形蛋白（homeoproteins）识别不同的调控元件，或以迥异方式结合同一调控元件。
超双胸（Ultrabithorax, UBX）、腹部-A（abdominal-A, ABD-A）及触角足（Antennapedia, ANTP）同源异形蛋白，在细胞培养共转染实验（cell culture cotransfection assay）中可差异化调控触角足P1启动子：UBX与ABD-A对P1产生抑制作用，而ANTP则激活P1的转录。P1启动子的两个区域均可赋予这种差异化调控模式。其中一个区域位于下游，其包含的同源异形蛋白结合位点环绕着一段被命名为BetBS的37碱基对（37-bp）区域。ANTP蛋白通过结合该位点激活转录，而UBX与ABD-A则通过BetBS激活转录，并借助侧翼结合位点阻断这一激活效应。由此可见，同源异形蛋白可结合同一调控元件，但作用方式截然不同。嵌合UBX-ANTP蛋白及UBX缺失衍生蛋白的实验结果证实，P1调控中的功能特异性主要由同源结构域（homeodomain）外侧的序列决定，其中蛋白质N端区域存在关键调控决定基序。
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