Coordinate regulation of downstream genes by extradenticle and the homeotic selector proteins.
Coordinate regulation of downstream genes by extradenticle and the homeotic selector proteins.
复制标题
通过外齿和同源异型选择蛋白协调下游基因的调节。
DOI：
10.1002/j.1460-2075.1994.tb06663.x
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Wieschaus,E
中科院分区：
文献类型：
--
作者：
Rauskolb,C;Wieschaus,E
果蝇外齿基因（exd）是人类原癌基因pbx 1的同源物，其突变通过改变同源异型选择基因活性的形态结果而引起同源异型转化。已经提出EXD通过促进选择者同源结构域蛋白对其下游靶的特异性而起作用。在这里，我们表明，exd确实需要适当的调节，至少有一些这些靶基因。在缺乏exd的胚胎中肠中，wingless，teashirt和decapentaplegic（dpp）的表达模式发生了变化，而它们各自的调节因子（abd-A，Antp和Ubx）的表达保持正常。通过检查exd胚胎中报告基因构建体的表达，更详细地研究了exd和Ubx对dpp的共调节。这些实验不仅确定了对exd应答的dpp调控区域，而且区分了exd在dpp调控中的两种功能。exd与Ubx一起通过最小的内脏中胚层增强子激活parsegment 7（PS 7）中的dpp表达，并且exd在PS 7之前抑制dpp表达。我们发现，即使UBX在exd胚胎中以高水平普遍表达，UBX也无法激活DPP增强子表达。因此，exd是同源异型选择蛋白调控靶基因的一个不可或缺的组成部分。
Mutations in the Drosophila gene extradenticle (exd), a homologue of the human proto‐oncogene pbx1, cause homeotic transformations by altering the morphological consequences of homeotic selector gene activity. exd has been proposed to act by contributing to the specificity of selector homeodomain proteins for their downstream targets. Here we show that exd is indeed required for the appropriate regulation of at least some of these target genes. Expression patterns of wingless, teashirt and decapentaplegic (dpp) are altered in the embryonic midgut of embryos lacking exd, while the expression of their respective regulators (abd‐A, Antp and Ubx) remains normal. Co‐regulation of dpp by exd and Ubx was investigated in greater detail by examining the expression of reporter constructs in exd embryos. These experiments not only define dpp regulatory regions responsive to exd, but also distinguish two functions of exd in the regulation of dpp. exd acts with Ubx to activate dpp expression in parasegment 7 (PS7), via a minimal visceral mesoderm enhancer, and exd represses dpp expression anterior to PS7. We show that even when Ubx is ubiquitously expressed at high levels in exd embryos, Ubx is incapable of activating dpp enhancer expression. Thus, exd is an indispensable component in target gene regulation by the homeotic selector proteins.