Post-translational Modifications of Trypanosoma cruzi Canonical and Variant Histones

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 acquir...

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Bibliographic Details
Published in:Journal of proteome research 2017-03, Vol.16 (3), p.1167-1179
Main Authors: Picchi, Gisele F. A, Zulkievicz, Vanessa, Krieger, Marco A, Zanchin, Nilson T, Goldenberg, Samuel, de Godoy, Lyris M. F
Format: Article
Language:English
Subjects:
Acetylation
Acylation
Epigenesis, Genetic
Histone Code
Histones - metabolism
Lysine - metabolism
Protein Processing, Post-Translational
Protozoan Proteins - genetics
Protozoan Proteins - metabolism
Serine - metabolism
Threonine - metabolism
Trypanosoma cruzi - genetics
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Summary: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.
ISSN:1535-3893
1535-3907
DOI:10.1021/acs.jproteome.6b00655