Post-translational Modifications of Trypanosoma cruzi Canonical and Variant Histones
Post-translational Modifications of Trypanosoma cruzi Canonical and Variant Histones
复制标题
DOI：
10.1021/acs.jproteome.6b00655
复制
发表时间：
2017-03-01
影响因子：
4.4
通讯作者：
de Godoy, Lyris M. F.
中科院分区：
文献类型：
--
作者：
Picchi, Gisele F. A.;Zulkievicz, Vanessa;de Godoy, Lyris M. F.
由克氏锥虫引起的恰加斯病仍然影响着世界各地数百万人。没有针对慢性恰加斯病的疫苗和治疗方法，急性期的化疗因疗效有限和严重副作用而受阻。寄生虫获得感染性并在不同宿主中存活的过程涉及基因表达的严格调控，主要是转录后调控。然而，锥虫的染色质结构/组织与其他真核生物相似，包括组蛋白变体和翻译后修饰。新出现的证据表明，表观遗传机制在这些寄生虫的生物学/发病机制中也起着重要作用，使表观遗传靶点成为药物发现的合适候选者。在这里，我们提出了第一个全面的T。cruzi典型组蛋白和变异组蛋白的研究表明，它的组蛋白编码可以像其他真核生物一样复杂。共鉴定了13种不同的修饰类型，包括相当新颖和不寻常的，如替代赖氨酸酰化，丝氨酸/苏氨酸乙酰化，和N-末端甲基化。一些组蛋白标记与其他生物体中描述的标记相关，表明可能存在类似的调节机制。然而，其他的则是T. cruzi或锥虫作为一个群体，并可能代表开发抗寄生虫药物的良好候选者。
Chagas disease, caused by Trypanosoma cruzi, still affects millions of people around the world. No vaccines nor treatment for chronic Chagas disease are available, and chemotherapy for the acute phase is hindered by limited efficacy and severe side effects. The processes by which the parasite acquires infectivity and survives in different hosts involve tight regulation of gene expression, mainly post transcriptionally. Nevertheless, chromatin structure/organization of trypanosomatids is similar to other eukaryotes, including histone variants and post-translational modifications. Emerging evidence suggests that epigenetic mechanisms also play an important role in the biology/pathogenesis of these parasites, making epigenetic targets suitable candidates to drug discovery. Here, we present the first comprehensive map of post-translational modifications of T. cruzi canonical and variant histones and show that its histone code can be as sophisticated as that of other eukaryotes. A total of 13 distinct modification types were identified, including rather novel and unusual ones such as alternative lysine acylations, serine/threonine acetylation, and N-terminal methylation. Some histone marks correlate to those described for other organisms, suggesting that similar regulatory mechanisms may be in place. Others, however, are unique to T. cruzi or to trypanosomatids as a group and might represent good candidates for the development of antiparasitic drugs.