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首页> 外文期刊>Journal of proteome research >Chromatin Proteomics Reveals Variable Histone Modifications during the Life Cycle of Trypanosoma cruzi
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Chromatin Proteomics Reveals Variable Histone Modifications during the Life Cycle of Trypanosoma cruzi

机译：染色质蛋白质组学揭示了克鲁斯锥虫生命周期中的可变组蛋白修饰。

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摘要

Histones are well-conserved proteins that form the basic structure of chromatin in eukaryotes and undergo several post-translational modifications, which are important for the control of transcription, replication, DNA damage repair, and chromosome condensation. In early branched organisms, histones are less conserved and appear to contain alternative sites for modifications, which could reveal evolutionary unique functions of histone modifications in gene expression and other chromatin-based processes. Here, by using high-resolution mass spectrometry, we identified and quantified histone post-translational modifications in two life cycle stages of Trypanosoma cruzi, the protozoan parasite that causes Chagas disease. We detected 44 new modifications, namely: 18 acetylations, seven monomethylations, seven dimethylations, seven trimethylations, and four phosphorylations. We found that replicative (epimastigote stage) contains more histone modifications than nonreplicative and infective parasites (trypomastigote stage). Acetylations of lysines at the C-terminus of histone H2A and methylations of lysine 23 of histone H3 were found to be enriched in trypomastigotes. In contrast, phosphorylation in serine 23 of H2B and methylations of lysine 76 of histone H3 predominates in proliferative states. The presence of one or two methylations in the lysine 76 was found in cells undergoing mitosis and cytokinesis, typical of proliferating parasites. Our findings provide new insights into the role of histone modifications related to the control of gene expression and cell-cycle regulation in an early divergent organism.
机译：组蛋白是保存完好的蛋白，可形成真核生物中染色质的基本结构，并经历几种翻译后修饰，这对于控制转录，复制，DNA损伤修复和染色体浓缩非常重要。在早期分支的生物中，组蛋白保守性较低，似乎包含修饰的替代位点，这可能揭示了组蛋白修饰在基因表达和其他基于染色质过程中的进化独特功能。在这里，通过使用高分辨率质谱，我们确定并量化了锥虫锥虫（Trychaos Cruzi）的两个生命周期阶段中的组蛋白翻译后修饰，锥虫锥虫是导致恰加斯病的原生动物寄生虫。我们检测到44个新的修饰，即：18个乙酰化，7个单甲基化，7个二甲基化，7个三甲基化和4个磷酸化。我们发现，复制性（ima虫阶段）比非复制性和感染性寄生虫（锥虫病阶段）包含更多的组蛋白修饰。发现组蛋白H2A的C端赖氨酸的乙酰化和组蛋白H3的赖氨酸23的甲基化都富含锥虫。相反，在增殖状态下，H2B的丝氨酸23的磷酸化和组蛋白H3的赖氨酸76的甲基化占优势。在经历有丝分裂和胞质分裂的细胞中发现了赖氨酸76中存在一个或两个甲基化，这是寄生虫的典型特征。我们的发现为组蛋白修饰在早期发散生物中与基因表达控制和细胞周期调控有关的作用提供了新见解。

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