Malmanche Nicolas, Clark Denise V
Department of Biology, University of New Brunswick, Fredericton, New Brunswick E3B 6E1, Canada.
Genetics. 2003 Aug;164(4):1419-33. doi: 10.1093/genetics/164.4.1419.
The first committed step in the purine de novo synthesis pathway is performed by amidophosphoribosyltransferase (EC 2.4.2.14) or Prat. Drosophila melanogaster Prat is an essential gene with a promoter that lacks a TATA-box and initiator element and has multiple transcription start sites with a predominant start site. To study the regulation of Prat expression in the adult eye, we used the Prat:bw reporter gene, in which the Prat coding region was replaced with the brown (bw) coding region. The pale-orange eye color of a single copy of Prat:bw prompted us to use a multicopy array of Prat:bw that was derived using P transposase mutagenesis and produces a darker-orange eye color in a bw(D); st genetic background. We used a 13-copy array of Prat:bw as a tool to recover dominant EMS-induced mutations that affect the expression of the transgene. After screening 21,000 F(1)s for deviation from the orange eye color, we isolated 23 dominant modifiers: 21 suppressors (1 Y-linked, 5 X-linked, 4 2-linked, and 11 3-linked) and 2 enhancers (1 2-linked and 1 3-linked). Quantification of their effect on endogenous Prat gene expression, using RT-PCR in young adult fly heads, identifies a subset of modifiers that are candidates for genes involved in regulating Prat expression.
嘌呤从头合成途径中的第一个关键步骤由酰胺磷酸核糖基转移酶(EC 2.4.2.14)或Prat执行。黑腹果蝇的Prat是一个必需基因,其启动子缺乏TATA框和起始元件,有多个转录起始位点,其中一个为主导起始位点。为了研究成年果蝇眼睛中Prat表达的调控,我们使用了Prat:bw报告基因,其中Prat编码区被棕色(bw)编码区取代。单拷贝Prat:bw呈现的浅橙色眼睛颜色促使我们使用通过P转座酶诱变获得的多拷贝Prat:bw阵列,该阵列在bw(D); st遗传背景下产生更深的橙色眼睛颜色。我们使用13拷贝的Prat:bw阵列作为工具来筛选影响转基因表达的显性EMS诱导突变。在对21,000只F(1)代果蝇进行橙色眼睛颜色偏差筛选后,我们分离出23个显性修饰因子:21个抑制因子(1个Y连锁、5个X连锁、4个第二染色体连锁和11个第三染色体连锁)和2个增强因子(1个第二染色体连锁和1个第三染色体连锁)。通过在年轻成年果蝇头部使用RT-PCR对它们对内源Prat基因表达的影响进行定量分析,确定了一部分修饰因子,它们可能是参与调控Prat表达的基因的候选者。