Histone modification analysis reveals common regulators of gene expression in liver and blood stage merozoites of Plasmodium parasites.
Histone modification analysis reveals common regulators of gene expression in liver and blood stage merozoites of Plasmodium parasites.
复制标题
DOI：
10.1186/s13072-023-00500-y
复制
发表时间：
2023-06-15
影响因子：
3.9
通讯作者：
中科院分区：
文献类型：
--
作者：
疟疾寄生虫的基因表达受到多种调控，包括组蛋白翻译后修饰（PTMs）。在红细胞内疟原虫的主要发育阶段，从入侵后的环阶段到分裂体阶段，基因调控机制已经得到了广泛的研究。然而，介导从一个宿主细胞到下一个宿主细胞的分裂子的基因调控是寄生虫生物学中一个未被充分研究的领域。在这里，我们试图通过RNA-seq和ChIP-seq对恶性疟原虫血期分裂体、分裂子和环以及伯氏疟原虫肝期分裂子的基因表达和相应的组蛋白PTM图谱进行表征。在肝脏和红细胞的分裂子中，我们发现了一个具有独特组蛋白PTM谱的基因子集，其特征是启动子中的H3K4me3缺失区域。这些基因在肝脏和红细胞的分裂子和环中上调，在蛋白质输出、翻译和宿主细胞重塑中起作用，并共享一个DNA基序。这些结果表明，在肝脏和血液阶段，类似的调节机制可能是merozoite形成的基础。我们还观察到H3K4me2沉积在红细胞分裂子中编码不同表面抗原的基因家族的基因体中，这可能促进了这些家族不同成员之间基因表达的转换。最后，H3K18me和H2K27me从基因表达中解耦，并在红细胞分裂体和分裂子的着丝粒周围富集，提示在分裂分裂过程中维持染色体组织的潜在作用。总之，我们的研究结果表明，基因表达和组蛋白景观的广泛变化发生在分裂体到环过渡期间，以促进生产性红细胞感染。肝脏和红细胞分裂子中转录程序的动态重塑使得这一阶段成为可能对肝脏和血液阶段都有活性的新型抗疟疾药物的有吸引力的靶点。在线版本包含补充材料，可在10.1186/s13072-023-00500-y获得。
Gene expression in malaria parasites is subject to various layers of regulation, including histone post-translational modifications (PTMs). Gene regulatory mechanisms have been extensively studied during the main developmental stages of Plasmodium parasites inside erythrocytes, from the ring stage following invasion to the schizont stage leading up to egress. However, gene regulation in merozoites that mediate the transition from one host cell to the next is an understudied area of parasite biology. Here, we sought to characterize gene expression and the corresponding histone PTM landscape during this stage of the parasite lifecycle through RNA-seq and ChIP-seq on P. falciparum blood stage schizonts, merozoites, and rings, as well as P. berghei liver stage merozoites. In both hepatic and erythrocytic merozoites, we identified a subset of genes with a unique histone PTM profile characterized by a region of H3K4me3 depletion in their promoter. These genes were upregulated in hepatic and erythrocytic merozoites and rings, had roles in protein export, translation, and host cell remodeling, and shared a DNA motif. These results indicate that similar regulatory mechanisms may underlie merozoite formation in the liver and blood stages. We also observed that H3K4me2 was deposited in gene bodies of gene families encoding variant surface antigens in erythrocytic merozoites, which may facilitate switching of gene expression between different members of these families. Finally, H3K18me and H2K27me were uncoupled from gene expression and were enriched around the centromeres in erythrocytic schizonts and merozoites, suggesting potential roles in the maintenance of chromosomal organization during schizogony. Together, our results demonstrate that extensive changes in gene expression and histone landscape occur during the schizont-to-ring transition to facilitate productive erythrocyte infection. The dynamic remodeling of the transcriptional program in hepatic and erythrocytic merozoites makes this stage attractive as a target for novel anti-malarial drugs that may have activity against both the liver and blood stages. The online version contains supplementary material available at 10.1186/s13072-023-00500-y.
登录
查看更多内容
影响因子：
16.6
作者：
Batinovic S;McHugh E;Chisholm SA;Matthews K;Liu B;Dumont L;Charnaud SC;Schneider MP;Gilson PR;de Koning-Ward TF;Dixon MWA;Tilley L
通讯作者：
Tilley L
影响因子：
6.7
作者：
Baer K;Klotz C;Kappe SH;Schnieder T;Frevert U
通讯作者：
Frevert U
影响因子：
16
作者：
Calo, Eliezer;Wysocka, Joanna
通讯作者：
Wysocka, Joanna
影响因子：
9.8
作者：
Bozdech, Zbynek;Llinas, Manuel;Pulliam, Brian Lee;Wong, Edith D;Zhu, Jingchun;DeRisi, Joseph L
通讯作者：
DeRisi, Joseph L
影响因子：
3.4
作者：
Blackman, Michael J.
通讯作者：
Blackman, Michael J.