Three-dimensional modeling of the P. falciparum genome during the erythrocytic cycle reveals a strong connection between genome architecture and gene expression.
Three-dimensional modeling of the P. falciparum genome during the erythrocytic cycle reveals a strong connection between genome architecture and gene expression.
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DOI：
10.1101/gr.169417.113
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发表时间：
2014-06
期刊：
影响因子：
7
通讯作者：
Le Roch KG
中科院分区：
文献类型：
--
作者：
Ay F;Bunnik EM;Varoquaux N;Bol SM;Prudhomme J;Vert JP;Noble WS;Le Roch KG
人类恶性疟原虫的发育受其复杂生命周期中基因表达的协调变化控制，但相应的调控机制尚未完全了解。为了研究疟原虫基因组结构与基因调控之间的关系，我们分析了恶性疟原虫红细胞（无性）周期中三个时间点的基因组结构。使用染色体构象捕获结合下一代测序技术（Hi-C），我们获得了高分辨率的染色体接触图，然后我们使用它来构建每个时间点的共有三维基因组结构。我们观察到着丝粒，端粒，核糖体DNA和毒力基因的强烈聚类，导致一个复杂的架构，不能用一个简单的体积排阻模型来解释。内部毒力基因簇在接触图谱中呈现结构域样结构，表明它们在基因组结构中起着重要作用。在红细胞周期的中途，在高度转录活性的滋养体阶段，基因组采用更开放的染色质结构，增加染色体混合。此外，我们观察到位于空间上接近抑制性亚端粒中心的基因表达减少，以及具有协调表达谱的不同寄生虫特异性基因组的共定位。总的来说，我们的研究结果表明恶性疟原虫空间基因组组织和基因表达之间有很强的关联。了解基因组构象动力学中涉及的分子过程可能有助于发现新的抗疟策略。
The development of the human malaria parasite Plasmodium falciparum is controlled by coordinated changes in gene expression throughout its complex life cycle, but the corresponding regulatory mechanisms are incompletely understood. To study the relationship between genome architecture and gene regulation in Plasmodium, we assayed the genome architecture of P. falciparum at three time points during its erythrocytic (asexual) cycle. Using chromosome conformation capture coupled with next-generation sequencing technology (Hi-C), we obtained high-resolution chromosomal contact maps, which we then used to construct a consensus three-dimensional genome structure for each time point. We observed strong clustering of centromeres, telomeres, ribosomal DNA, and virulence genes, resulting in a complex architecture that cannot be explained by a simple volume exclusion model. Internal virulence gene clusters exhibit domain-like structures in contact maps, suggesting that they play an important role in the genome architecture. Midway during the erythrocytic cycle, at the highly transcriptionally active trophozoite stage, the genome adopts a more open chromatin structure with increased chromosomal intermingling. In addition, we observed reduced expression of genes located in spatial proximity to the repressive subtelomeric center, and colocalization of distinct groups of parasite-specific genes with coordinated expression profiles. Overall, our results are indicative of a strong association between the P. falciparum spatial genome organization and gene expression. Understanding the molecular processes involved in genome conformation dynamics could contribute to the discovery of novel antimalarial strategies.
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影响因子：
6.7
作者：
Ganesan K;Ponmee N;Jiang L;Fowble JW;White J;Kamchonwongpaisan S;Yuthavong Y;Wilairat P;Rathod PK
通讯作者：
Rathod PK
影响因子：
46.9
作者：
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--
α-珠蛋白基因结构域的三维折叠揭示了染色质球的形成。
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
14.9
作者：
Balaji S;Babu MM;Iyer LM;Aravind L
通讯作者：
Aravind L
影响因子：
64.8
作者：
Freitas-Junior, LH;Bottius, E;Scherf, A
通讯作者：
Scherf, A