Alterations in local chromatin environment are involved in silencing and activation of subtelomeric var genes in Plasmodium falciparum.
Alterations in local chromatin environment are involved in silencing and activation of subtelomeric var genes in Plasmodium falciparum.
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DOI：
10.1111/j.1365-2958.2007.05899.x
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发表时间：
2007-10
影响因子：
3.6
通讯作者：
Cowman, Alan F
中科院分区：
文献类型：
--
作者：
Voss, Till S;Tonkin, Christopher J;Marty, Allison J;Thompson, Jennifer K;Healer, Julie;Crabb, Brendan S;Cowman, Alan F
恶性疟原虫红细胞膜蛋白1（PfEMP 1）是由var基因家族编码的一种抗原性变异蛋白，在恶性疟原虫慢性感染和重症疟疾中起重要作用。每个寄生虫只有一个var基因转录，表观遗传控制机制是这种互斥转录策略的基础。我们发现，亚端粒upsB变异基因启动子进行附加体默认沉默，启动子激活是足够的沉默所有其他家庭成员。然而，当它们被放置在第二个活性var启动子的下游时，它们默认是活性的，这强调了局部染色质环境和核区室化在var启动子调控中的重要性。覆盖upsB启动子中SPE2重复序列的天然染色质对核酸酶消化具有抗性，并且将这些调控元件插入异源启动子中会导致核小体组织和启动子阻遏的局部改变。我们的研究结果表明，一个共同的逻辑基础上的所有变异基因的转录控制，并有重要的影响，我们了解的表观遗传过程中参与调控这个主要的毒力基因家族。
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the var gene family, undergoes antigenic variation and plays an important role in chronic infection and severe malaria. Only a single var gene is transcribed per parasite, and epigenetic control mechanisms are fundamental in this strategy of mutually exclusive transcription. We show that subtelomeric upsB var gene promoters carried on episomes are silenced by default, and that promoter activation is sufficient to silence all other family members. However, they are active by default when placed downstream of a second active var promoter, underscoring the significance of local chromatin environment and nuclear compartmentalization in var promoter regulation. Native chromatin covering the SPE2-repeat array in upsB promoters is resistant to nuclease digestion, and insertion of these regulatory elements into a heterologous promoter causes local alterations in nucleosomal organization and promoter repression. Our findings suggest a common logic underlying the transcriptional control of all var genes, and have important implications for our understanding of the epigenetic processes involved in the regulation of this major virulence gene family.