人类疟疾寄生虫的性差异化是由脂代谢和基因素甲基化之间的竞争调节的
Chantal T Harris1,2, Xinran Tong1,3, Riward Campelo1
1Department of Microbiology and Immunology, Weill Cornell Medicine, New York, NY, USA.
Nature microbiology
|June 5, 2023
概括
疟疾寄生虫的性分化是由营养的可用性来调节的. 类胆前体的稀缺性改变了S-adenosylmethionine的使用,影响了关键的AP2-G转录因子的表观遗传沉默.
科学领域:
- 分子寄生虫学 分子寄生虫学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 代谢调节 代谢调节 代谢调节
背景情况:
- 疟疾寄生虫Plasmodium falciparum的生存取决于无性复制和通过异性细胞发育传播.
- 在P. falciparum中,性差异是通过AP2-G转录因子进行表观遗传控制的,该转录因子由一个沉默的位置调节.
- 之前的研究表明,脂前体和雌激细胞生产之间存在联系,但机制仍然不清楚.
研究的目的:
- 阐明将细胞外脂前体连接到P. falciparum中AP2-G的表观遗传调节的分子机制.
- 了解新陈代谢状态如何影响疟疾寄生虫的性别差异化决定.
主要方法:
- 使用了分子遗传学技术的组合.
- 进行了全面的代谢分析.
- 进行了染色体概况研究.
主要成果:
- 确定了S-adenosylmethionine (SAM) 作为关键调解物的代谢竞争.
- 证明了组胺甲基转移酶和甲胺甲基转移酶对SAM进行竞争.
- 表明稀缺的甲基胆前体增加了SAM消耗以进行 de novo 合成,损害了基因素甲基化和升调 AP2-G,从而促进了性差异化.
结论:
- 在P. falciparum.中建立了营养素可用性 (酸胆前体) 和性差异化表观遗传控制之间的机制联系.
- 解释了LysoPC和胆水平如何影响AP2-G位点的染色质状态.
- 提供了对疟疾寄生虫传播调节的关键见解.
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