Plasmodium falciparum var genes are regulated by two regions with separate promoters, one upstream of the coding region and a second within the intron
Plasmodium falciparum var genes are regulated by two regions with separate promoters, one upstream of the coding region and a second within the intron
复制标题
DOI：
10.1074/jbc.m213065200
复制
发表时间：
2003-09-05
影响因子：
4.8
通讯作者：
Deitsch, KW
中科院分区：
文献类型：
--
作者：
Calderwood, MS;Gannoun-Zaki, L;Deitsch, KW
恶性疟原虫疟疾寄生虫的抗原变异是由多拷贝var基因家族成员之间的表达转换引起的。该家族受到等位基因排斥，通过等位基因排斥，特定基因表达，而家族的其余部分保持转录沉默。来自报告构建体的证据表明，var基因沉默涉及var内含子和上游元件之间的合作相互作用，并需要通过细胞周期的S期的寄生虫的过渡。这些发现暗示染色质组装在调节var基因表达和抗原变异的过程中。在这里，我们的特点是var内含子和它内部的元件是必要的var转录沉默。变异内含子的排列显示出高度保守的结构，由三个具有不同碱基对组成的离散区域组成。中间区域富含AT，足以沉默相关的var启动子。构建体，包括一个典型的var内含子上游的报告基因或药物选择性标记显示，内含子也具有启动子活性，大概提供了一个解释的起源，以前描述的var“无菌”的成绩单。使内含子的启动子活性丧失的缺失也消除了其作为沉默子的功能。这些发现表明，这两个启动子区域之间的相互作用和不育转录本的产生在调节var基因表达中起着重要作用。
Antigenic variation in Plasmodium falciparum malaria parasites results from switches in expression among members of the multicopy var gene family. This family is subject to allelic exclusion by which particular genes are expressed while the rest of the family remains transcriptionally silent. Evidence from reporter constructs indicates that var gene silencing involves a cooperative interaction between the var intron and an upstream element and requires transition of the parasites through S-phase of the cell cycle. These findings implicate chromatin assembly in the process of regulating var gene expression and antigenic variation. Here we characterize the var intron and the elements within it that are necessary for var transcriptional silencing. Alignments of var introns show a highly conserved structure that consists of three discreet regions with distinct base pair compositions. The middle region is highly AT-rich and is sufficient to silence an associated var promoter. Constructs that include a typical var intron upstream of a reporter gene or drug-selectable marker reveal that the intron also possesses promoter activity, presumably providing an explanation for the origin of the previously described var "sterile" transcripts. Deletions that disable the promoter activity of the intron also eliminate its ability to function as a silencer. These findings suggest that interactions between the regions of these two promoters and the generation of the sterile transcripts play a significant role in regulating var gene expression.