The human malaria parasite genome is configured into thousands of coexpressed linear regulatory units.
The human malaria parasite genome is configured into thousands of coexpressed linear regulatory units.
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DOI：
10.1016/j.jgg.2020.08.005
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发表时间：
2020-09-20
影响因子：
5.9
通讯作者：
Jiang, Rays H. Y.
中科院分区：
文献类型：
--
作者：
Wang, Chengqi;Gibbons, Justin;Adapa, Swamy R.;Oberstaller, Jenna;Liao, Xiangyun;Zhang, Min;Adams, John H.;Jiang, Rays H. Y.
人类疟疾寄生虫恶性疟原虫在蚊子和人类截然不同的宿主环境中繁衍生息，仅具有有限的转录因子。恶性疟原虫基因组中的调控元件或其靶基因的性质仍然难以捉摸。在这里，我们发现这种真核寄生虫在血液感染期间使用一种有效的方式最大限度地利用遗传和表观遗传调控来形成调控单元（RU）。随着时间的推移，位于同一 RU 中的基因往往具有相同的表达模式，并且与沿着调控元件的开放染色质相关。为了精确定义和量化这些 RU，开发了一种新颖的隐马尔可夫模型，通过整合表达和表观遗传证据来捕获全基因组范围内的调控结构。我们成功识别了数千个 RU，并与之前的发现进行了交叉验证。我们发现更多参与红细胞（RBC）侵袭的基因与PfAP2-I（AP2-I）转录因子位于同一RU中，表明AP2-I负责调节红细胞侵袭。我们的研究为紧凑的真核基因组提供了一种调控机制，并为恶性疟原虫红细胞内阶段的体内转录调控提供了新的见解。
The human malaria parasite Plasmodium falciparum thrives in radically different host environments in mosquitoes and humans, with only a limited set of transcription factors. The nature of regulatory elements or their target genes in the P. falciparum genome remains elusive. Here, we found that this eukaryotic parasite uses an efficient way to maximally use genetic and epigenetic regulation to form regulatory units (RUs) during blood infections. Genes located in the same RU tend to have the same pattern of expression over time and are associated with open chromatin along regulatory elements. To precisely define and quantify these RUs, a novel hidden Markov model was developed to capture the regulatory structure in a genome-wide fashion by integrating expression and epigenetic evidence. We successfully identified thousands of RUs and cross-validated with previous findings. We found more genes involved in red blood cell (RBC) invasion located in the same RU as the PfAP2-I (AP2-I) transcription factor, demonstrating that AP2-I is responsible for regulating RBC invasion. Our study has provided a regulatory mechanism for a compact eukaryotic genome and offers new insights into the in vivo transcriptional regulation of the P. falciparum intraerythrocytic stage.
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