Saraf Anita, Cervantes Serena, Bunnik Evelien M, Ponts Nadia, Sardiu Mihaela E, Chung Duk-Won D, Prudhomme Jacques, Varberg Joseph M, Wen Zhihui, Washburn Michael P, Florens Laurence, Le Roch Karine G
Stowers Institute for Medical Research , 1000 E. 50th Street, Kansas City, Missouri 64110, United States.
Department of Cell Biology and Neuroscience, University of California , 900 University Avenue, Riverside, California 92521, United States.
J Proteome Res. 2016 Aug 5;15(8):2787-801. doi: 10.1021/acs.jproteome.6b00366. Epub 2016 Jun 24.
A major obstacle in understanding the complex biology of the malaria parasite remains to discover how gene transcription is controlled during its life cycle. Accumulating evidence indicates that the parasite's epigenetic state plays a fundamental role in gene expression and virulence. Using a comprehensive and quantitative mass spectrometry approach, we determined the global and dynamic abundance of histones and their covalent post-transcriptional modifications throughout the intraerythrocytic developmental cycle of Plasmodium falciparum. We detected a total of 232 distinct modifications, of which 160 had never been detected in Plasmodium and 88 had never been identified in any other species. We further validated over 10% of the detected modifications and their expression patterns by multiple reaction monitoring assays. In addition, we uncovered an unusual chromatin organization with parasite-specific histone modifications and combinatorial dynamics that may be directly related to transcriptional activity, DNA replication, and cell cycle progression. Overall, our data suggest that the malaria parasite has a unique histone modification signature that correlates with parasite virulence.
理解疟原虫复杂生物学特性的一个主要障碍仍然是发现其生命周期中基因转录是如何被调控的。越来越多的证据表明，疟原虫的表观遗传状态在基因表达和毒力方面起着根本性作用。我们采用全面且定量的质谱方法，确定了恶性疟原虫红细胞内发育周期中组蛋白及其共价转录后修饰的整体动态丰度。我们总共检测到232种不同的修饰，其中160种从未在疟原虫中被检测到，88种从未在任何其他物种中被鉴定到。我们通过多反应监测分析进一步验证了超过10%的检测到的修饰及其表达模式。此外，我们发现了一种不同寻常的染色质组织，其具有寄生虫特异性的组蛋白修饰和组合动态，这可能与转录活性、DNA复制和细胞周期进程直接相关。总体而言，我们的数据表明疟原虫具有与寄生虫毒力相关的独特组蛋白修饰特征。
