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通过增强子检测鉴定同源异型基因触角足的靶基因。

Identification of target genes of the homeotic gene Antennapedia by enhancer detection.

作者信息

Wagner-Bernholz J T, Wilson C, Gibson G, Schuh R, Gehring W J

机构信息

Biozentrum, University of Basel, Switzerland.

出版信息

Genes Dev. 1991 Dec;5(12B):2467-80. doi: 10.1101/gad.5.12b.2467.

DOI:10.1101/gad.5.12b.2467
PMID:1684334
Abstract

Localized expression of the homeotic gene Antennapedia (Antp) in Drosophila melanogaster is required for normal development of the thoracic segments. When the Antp gene is expressed ectopically in the larval primordium of the antenna, the antennal imaginal disc, the developmental fate of the disc is switched and the adult antenna is transformed to a mesothoracic leg. We screened approximately 550 different fly strains carrying single copies of an enhancer-detector transposon to identify regulatory elements and corresponding genes that are either activated or repressed in antennal discs in response to this transformation. Several regulatory elements that are either direct or indirect targets of Antp were found. One transposant that expresses the reporter gene (lacZ) in the antennal disc, but not in the leg disc, was studied in more detail. The enhancer detector in this strain is located near a similarly regulated gene at the spalt (sal) locus, which encodes a homeotic function involved in embryonic head and tail development. The expression of this newly discovered gene, spalt major (salm) is strongly repressed in gain-of-function mutants that express Antp in the antennal disc. Recessive loss-of-function mutations (Antp-) have the opposite developmental effect; they cause the differentiation of antennal structures in the second leg disc. Accordingly, salm is derepressed in clones of homozygous Antp- cells. Therefore, we conclude that Antp negatively regulates salm. The time course of the interaction and reporter gene fusion experiments suggests (but does not prove) a direct interaction between Antp and cis-regulatory elements of salm. Our analysis of several enhancer-detector strains suggests that the basic patterning information in the antennal and leg imaginal discs is very similar.

摘要

同源异型基因触角足基因(Antp)在黑腹果蝇中的局部表达是胸节正常发育所必需的。当Antp基因在触角的幼虫原基即触角成虫盘异位表达时,成虫盘的发育命运会发生改变,成虫触角会转变为中胸腿。我们筛选了约550种携带增强子检测转座子单拷贝的不同果蝇品系,以鉴定在触角成虫盘响应这种转变时被激活或抑制的调控元件及相应基因。发现了几个作为Antp直接或间接靶标的调控元件。对一个在触角成虫盘中表达报告基因(lacZ)但在腿成虫盘中不表达的转座子进行了更详细的研究。该品系中的增强子检测元件位于spalt(sal)基因座处一个受类似调控的基因附近,该基因编码参与胚胎头部和尾部发育的同源异型功能。在触角成虫盘中表达Antp的功能获得性突变体中,这个新发现的基因spalt major(salm)的表达受到强烈抑制。隐性功能丧失突变(Antp-)具有相反的发育效应;它们导致第二腿成虫盘中触角结构的分化。因此,在纯合Antp-细胞克隆中salm的表达去抑制。所以,我们得出结论,Antp对salm起负调控作用。相互作用的时间进程和报告基因融合实验表明(但未证明)Antp与salm的顺式调控元件之间存在直接相互作用。我们对几个增强子检测品系的分析表明,触角和腿成虫盘中的基本模式形成信息非常相似。

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