The chromatin bound proteome of the human malaria parasite

The chromatin bound proteome of the human malaria parasite
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DOI:
10.1099/mgen.0.000327
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发表时间:
2020-02-01
期刊:
影响因子:
3.9
通讯作者:
Le Roch, Karine G.
Le Roch, Karine G.
中科院分区:
生物学2区
文献类型:
--
作者:
Batugedara, Gayani;Lu, Xueqing M.;Le Roch, Karine G.

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蛋白质与DNA的相互作用是介导诸如基因表达等过程的基础。DNA复制和基因组完整性的维持。越来越多的证据表明,顶端复合体寄生虫(如恶性疟原虫)的染色质是高度组织化的,这种结构为转录调控提供了一种表观遗传机制。为了研究寄生虫染色质结构是如何被调节的,我们使用12个不同的真核生物基因组进行了比较基因组学分析。我们确定了保守的和寄生虫特异性的染色质相关结构域(CADs)和蛋白质(CAPs)。然后,我们使用染色质富集蛋白质组学(ChEP)方法实验捕获恶性疟原虫的cap。蛋白质组学数据集的拓扑评分分析揭示了caad和cap的阶段特异性富集。最后,我们鉴定了两个候选的cap:一个是3号染色体结构维持蛋白的保守同源物,另一个是聚类核蛋白的同源物,聚类核蛋白是一种功能类似于动物核层蛋白的植物样蛋白。总的来说,我们的研究结果提供了顶复合体中CAPs的全面概述,并有助于我们理解这些致命寄生虫中调节染色质结构和基因组结构的复杂分子成分。
Proteins interacting with DNA are fundamental for mediating processes such as gene expression. DNA replication and maintenance of genome integrity. Accumulating evidence suggests that the chromatin of apicomplexan parasites, such as Plasmodium falciparum, is highly organized, and this structure provides an epigenetic mechanism for transcriptional regulation. To investigate how parasite chromatin structure is being regulated, we undertook comparative genomics analysis using 12 distinct eukaryotic genomes. We identified conserved and parasite-specific chromatin-associated domains (CADs) and proteins (CAPs). We then used the chromatin enrichment for proteomics (ChEP) approach to experimentally capture CAPs in P falciparum. A topological scoring analysis of the proteomics dataset revealed stage-specific enrichments of CADs and CAPs. Finally, we characterized, two candidate CAPs: a conserved homologue of the structural maintenance of chromosome 3 protein and a homologue of the crowded-like nuclei protein, a plant-like protein functionally analogous to animal nuclear lamina proteins. Collectively, our results provide a comprehensive overview of CAPs in apicomplexans, and contribute to our understanding of the complex molecular components regulating chromatin structure and genome architecture in these deadly parasites.