A model for extradenticle function as a switch that changes HOX proteins from repressors to activators
A model for extradenticle function as a switch that changes HOX proteins from repressors to activators
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DOI：
10.1093/emboj/16.8.2032
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发表时间：
1997-04
期刊：
影响因子：
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通讯作者：
J. Pinsonneault;B. Florence;H. Vaessin;W. McGinnis
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文献类型：
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作者：
J. Pinsonneault;B. Florence;H. Vaessin;W. McGinnis
果蝇 EXD 蛋白及其哺乳动物对应物 PBX 蛋白已被认为在 HOX 靶点选择性中发挥作用。在这里，我们表明 exd 功能是后头 Dfd 表达的自动激活阶段所必需的。改变小自激活元件对 EXD 蛋白的亲和力的突变会导致元件胚胎活性的相应变化。我们的数据表明，EXD 和 DFD 蛋白直接激活上颌细胞中的该元件，而不协同结合到专门的异二聚体结合位点。基于在 exd 突变体胚胎中观察到的同源转化类型和基因表达变化，我们提出了 EXD/PBX 作用的新模型，其中这些蛋白是 HOX 蛋白转录激活功能所必需的，但对于 HOX 转录抑制功能来说是可有可无的。尽管在某些情况下，HOX 蛋白相对于另一个蛋白对特定靶基因的选择可以通过 EXD 对 HOX 结合特异性的选择性调节来解释，但我们赞成这样的观点，即 EXD 在更一般的意义上与大多数 HOX 蛋白相互作用，将它们转变为能够转录激活的状态。
The Drosophila EXD protein and its mammalian counterparts, the PBX proteins, have been proposed to function in HOX target selectivity. Here we show that exd function is required for the autoactivation phase of Dfd expression in the posterior head. Mutations that change the affinity of a small autoactivation element for EXD protein result in corresponding changes in the element's embryonic activity. Our data suggest that the EXD and DFD proteins directly activate this element in maxillary cells without cooperatively binding to a specialized heterodimer binding site. Based on the types of homeotic transformations and changes in gene expression observed in exd mutant embryos, we propose a new model for EXD/PBX action in which these proteins are required for HOX protein transcriptional activation functions, but dispensable for HOX transcriptional repression functions. Although the selection of a specific target gene by a HOX protein versus another may be explained in some cases by the selective modulation of HOX binding specificity by EXD, we favor the idea that EXD interacts in a more general sense with most HOX proteins to switch them into a state where they are capable of transcriptional activation.