Erasing the epigenetic memory and beginning to switch--the onset of antigenic switching of var genes in Plasmodium falciparum.
Erasing the epigenetic memory and beginning to switch--the onset of antigenic switching of var genes in Plasmodium falciparum.
复制标题
DOI：
10.1371/journal.pone.0034168
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dzikowski R
中科院分区：
文献类型：
--
作者：
Fastman Y;Noble R;Recker M;Dzikowski R
恶性疟原虫中的抗原变异受var基因家族成员之间的转录开关调节，每个基因以相互排斥的方式表达并编码统称为PfEMP 1的表面抗原的不同变体。当第一个裂殖子从肝脏排出并开始它们在红细胞内的无性增殖时，抗原转换开始。通过消除表观遗传记忆，我们创造了没有var背景的寄生虫，类似于从没有var基因表达的肝脏中排出的裂殖子。创建一个空变量背景使我们能够调查在感染的早期阶段的抗原开关的发病。在转换开始时，var转录模式是异质的，许多基因以低水平转录，包括upsA var，这是一种与严重疟疾有关的亚型，在生长的培养物中很少被激活。对随后的体外开关的分析表明，基因开启或关闭的概率与其染色体位置或启动子类型本身无关，而是与每个基因的内在特性有关。我们的结论是，var开关是由基因特异性相关的开关率，而不是一般的启动子类型或基因座相关的开关率。此外，我们表明，微调减少在var转录增加其开关率，表明转录扰动可以改变抗原开关。
Antigenic variation in Plasmodium falciparum is regulated by transcriptional switches among members of the var gene family, each expressed in a mutually exclusive manner and encoding a different variant of the surface antigens collectively named PfEMP1. Antigenic switching starts when the first merozoites egress from the liver and begin their asexual proliferation within red blood cells. By erasing the epigenetic memory we created parasites with no var background, similar to merozoites that egress from the liver where no var gene is expressed. Creating a null-var background enabled us to investigate the onset of antigenic switches at the early phase of infection. At the onset of switching, var transcription pattern is heterogeneous with numerous genes transcribed at low levels including upsA vars, a subtype that was implicated in severe malaria, which are rarely activated in growing cultures. Analysis of subsequent in vitro switches shows that the probability of a gene to turn on or off is not associated with its chromosomal position or promoter type per se but on intrinsic properties of each gene. We concluded that var switching is determined by gene specific associated switch rates rather than general promoter type or locus associated switch rates. In addition, we show that fine tuned reduction in var transcription increases their switch rate, indicating that transcriptional perturbation can alter antigenic switching.
登录
查看更多内容
旋钮阳性和旋钮阴性疟原虫恶性疟原虫在感染红细胞表面的菌株特异性疟疾抗原的表达上有所不同。
影响因子：
15.3
作者：
Aley, S B;Sherwood, J A;Howard, R J
通讯作者：
Howard, R J
DOI：
10.1038/nrmicro2145
发表时间：
2009-07
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
影响因子：
14.9
作者：
Deitsch, KW;Driskill, CL;Wellems, TE
通讯作者：
Wellems, TE
影响因子：
64.5
作者：
BARUCH, DI;PASLOSKE, BL;HOWARD, RJ
通讯作者：
HOWARD, RJ
影响因子：
4.8
作者：
Calderwood, MS;Gannoun-Zaki, L;Deitsch, KW
通讯作者：
Deitsch, KW