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寄生虫特异性基因家族在疟原虫传播阶段的基因组组织变化。

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

机构信息

Department of Microbiology, Immunology & Molecular Genetics, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA.

Department of Molecular, Cell and Systems Biology, University of California Riverside, 900 University Ave, Riverside, CA, 92521, USA.

出版信息

Nat Commun. 2018 May 15;9(1):1910. doi: 10.1038/s41467-018-04295-5.

Abstract

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.

摘要

疟原虫在其各个生命周期阶段的发育是由基因表达的变化来协调的。我们之前曾表明,疟原虫基因组的三维结构与红细胞内复制周期中的基因表达密切相关。在这里,我们分析了疟原虫和疟原虫传播阶段的基因组组织。在发病机制和免疫逃避、宿主细胞入侵、性分化以及基因表达的主要调控因子中,基因的定位和相互作用发生了重大变化。此外,我们观察到参与宿主细胞重塑的端粒异染色质周围的重组。耗竭异染色质蛋白 1(PfHP1)导致毒力基因之间的相互作用丧失,证实 PfHP1 对于维持抑制中心是必需的。我们的研究结果表明,人类疟原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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1c44/5954139/55256af37015/41467_2018_4295_Fig1_HTML.jpg

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