Changes in genome organization of parasite-specific gene families during the Plasmodium transmission stages.

Changes in genome organization of parasite-specific gene families during the Plasmodium transmission stages.
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DOI:
10.1038/s41467-018-04295-5
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发表时间:
2018-05-15
影响因子:
16.6
通讯作者:
Le Roch KG
Le Roch KG
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Bunnik EM;Cook KB;Varoquaux N;Batugedara G;Prudhomme J;Cort A;Shi L;Andolina C;Ross LS;Brady D;Fidock DA;Nosten F;Tewari R;Sinnis P;Ay F;Vert JP;Noble WS;Le Roch KG

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疟疾寄生虫在其各个生命周期阶段的发展是通过基因表达的变化来协调的。我们以前表明,恶性疟原虫基因组的三维组织与其在红细胞内的复制周期中的基因表达密切相关。在这里,我们分析了恶性疟原虫和间日疟原虫传播阶段的基因组组织。主要的变化发生在参与发病机制和免疫逃避、宿主细胞侵袭、性分化和基因表达调控的基因的定位和相互作用中。此外,我们观察到重组亚端粒异染色质周围的基因参与宿主细胞重塑。异染色质蛋白1(PfHP 1)的耗尽导致毒力基因之间的相互作用的损失,证实PfHP 1是维持阻遏中心所必需的。我们的研究结果表明,人类疟疾寄生虫的三维基因组结构与整个生命周期中特定基因家族的转录活性密切相关。疟疾寄生虫的发育由基因表达的协调变化控制。在这里,作者表明,人类疟疾寄生虫的三维基因组结构与恶性疟原虫和间日疟原虫寄生虫整个生命周期中特定基因家族的转录活性密切相关。
The development of malaria parasites throughout their various life cycle stages is coordinated by changes in gene expression. We previously showed that the three-dimensional organization of the Plasmodium falciparum genome is strongly associated with gene expression during its replication cycle inside red blood cells. Here, we analyze genome organization in the P. falciparum and P. vivax transmission stages. Major changes occur in the localization and interactions of genes involved in pathogenesis and immune evasion, host cell invasion, sexual differentiation, and master regulation of gene expression. Furthermore, we observe reorganization of subtelomeric heterochromatin around genes involved in host cell remodeling. Depletion of heterochromatin protein 1 (PfHP1) resulted in loss of interactions between virulence genes, confirming that PfHP1 is essential for maintenance of the repressive center. Our results suggest that the three-dimensional genome structure of human malaria parasites is strongly connected with transcriptional activity of specific gene families throughout the life cycle. The development of malaria parasites is controlled by coordinated changes in gene expression. Here, the authors show that the three-dimensional genome structure of human malaria parasites is strongly connected with transcriptional activity of specific gene families throughout the life cycles of Plasmodium falciparum and Plasmodium vivax parasites.
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