The function of histone H3 lysine 76 methylation in host-induced differentiation in Trypanosoma brucei

组蛋白 H3 赖氨酸 76 甲基化在布氏锥虫宿主诱导分化中的作用

• 批准号: 61273351
• 负责人: Professor Dr. Christian Janzen
• 金额: --
• 依托单位: Lehrstuhl für Zell- und Entwicklungsbiologie (Zoologie I)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/61273351?language=en
• 关键词: function; histone; H3; lysine; 76

Trypanosomes are mammalian pathogens with a complex parasitic life cycle in different hosts. Changes in gene expression profiles that result in specialized life cycle stages are crucial to adapt to very different host environments. Trypanosomes mainly regulate mRNA levels by posttranscriptional mechanisms. Nevertheless, there is increasing evidence that changes in chromatin structure are correlated with differential gene activity during stage differentiation. Furthermore, trypanosome histones carry multiple post-translational modifications, some of which are involved in transcriptional regulation in other organisms. The first direct evidence that histone modifications are involved in the differentiation process was provided by targeted deletion of the histone methyltransferase DOT1B which resulted in the inability of bloodstream stage parasites to differentiate to fly midgut stages. In this project, we will investigate changes in the nuclear architecture during host-induced differentiation, specifically the subnuclear distribution of histone modifications, and the assignment of specific modifications to the activity status of differentially regulated genes. We will test the hypothesis that chromatin remodeling is involved in the regulation of gene expression triggered by the host environment.

锥虫是哺乳动物病原体，在不同宿主中具有复杂的寄生生活史。基因表达谱的变化，导致专门的生命周期阶段是至关重要的，以适应非常不同的宿主环境。锥虫主要通过转录后机制调节mRNA水平。然而，越来越多的证据表明，染色质结构的变化与阶段分化过程中的差异基因活性相关。此外，锥虫组蛋白携带多种翻译后修饰，其中一些参与其他生物体中的转录调控。组蛋白甲基转移酶DOT1B的靶向缺失提供了组蛋白修饰参与分化过程的第一个直接证据，这导致血流阶段寄生虫无法分化为苍蝇中肠阶段。在这个项目中，我们将研究在宿主诱导分化过程中的核结构的变化，特别是组蛋白修饰的亚核分布，以及差异调节基因的活性状态的特定修饰的分配。我们将测试的假设，染色质重塑是在宿主环境触发的基因表达调控参与。