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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Improvements on the quantitative analysis of Trypanosoma cruzi histone post translational modifications: Study of changes in epigenetic marks through the parasite's metacyclogenesis and life cycle

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de Lima, Loyze P. [1, 2] ; Poubel, Saloe Bispo [1, 2, 3] ; Yuan, Zuo-Fei [4] ; Roson, Juliana Nunes [1, 2] ; de Luna Vitorino, Francisca Nathalia [1, 2] ; Holetz, Fabiola Barbieri [3] ; Garcia, Benjamin A. [4] ; Chagas da Cunha, Julia Pinheiro [1, 2]
Total Authors: 8
[1] Inst Butantan, Lab Ciclo Celular, Sao Paulo, SP - Brazil
[2] Inst Butantan, Ctr Toxins Immune Response & Cell Signaling CeTIC, Sao Paulo, SP - Brazil
[3] Fiocruz MS, Inst Carlos Chagas, Rua Algacyr Munhoz Mader, 3775 CIC, BR-81350010 Curitiba, PR - Brazil
[4] Univ Penn, Perelman Sch Med, Dept Biochem & Biophys, Epigenet Inst, Philadelphia, PA 19104 - USA
Total Affiliations: 4
Document type: Journal article
Source: JOURNAL OF PROTEOMICS; v. 225, APR 15 2020.
Web of Science Citations: 0

Trypanosome histone N-terminal sequences are very divergent from the other eukaryotes, although they are still decorated by post-translational modifications (PTMs). Here, we used a highly robust workflow to analyze histone PTMs in the parasite Trypanosoma cruzi using mass spectrometry-based (MS-based) data-independent acquisition (DIA). We adapted the workflow for the analysis of the parasite's histone sequences by modifying the software EpiProfile 2.0, improving peptide and PTM quantification accuracy. This workflow could now be applied to the study of 141 T. cruzi modified histone peptides, which we used to investigate the dynamics of histone PTMs along the metacyclogenesis and the life cycle of T. cruzi. Global levels of histone acetylation and methylation fluctuates along metacyclogenesis, however most critical differences were observed between parasite life forms. More than 66 histone PTM changes were detected. Strikingly, the histone PTM pattern of metacyclic trypomastigotes is more similar to epimastigotes than to cellular trypomastigotes. Finally, we highlighted changes at the H4 N-terminus and at H3K76 discussing their impact on the trypanosome biology. Altogether, we have optimized a workflow easily applicable to the analysis of histone PTMs in T. cruzi and generated a dataset that may shed lights on the role of chromatin modifications in this parasite. Significance: Trypanosomes are unicellular parasites that have divergent histone sequences, no chromosome condensation and a peculiar genome/gene regulation. Genes are transcribed from divergent polycistronic regions and post-transcriptional gene regulation play major role on the establishment of transcripts and protein levels. In this regard, the fact that their histones are decorated with multiple PTMs raises interesting questions about their role. Besides, this digenetic organism must adapt to different environments changing its metabolism accordingly. As metabolism and epigenetics are closely related, the study of histone PTMs in trypanosomes may enlighten this strikingly, and not yet fully understood, interplay. From a biomedical perspective, the comprehensive study of molecular mechanisms associated to the metacyclogenesis process is essential to create better strategies for controlling Chagas disease. (AU)

FAPESP's process: 18/21785-0 - Analysis of Orc1/Cdc6-DNA interaction during the life cycle of Trypanosoma cruzi
Grantee:Loyze Paola Oliveira de Lima
Support Opportunities: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 17/06104-3 - Functional analysis of Trypanosoma Cruzi histone H2B variant
Grantee:Julia Pinheiro Chagas da Cunha
Support Opportunities: Regular Research Grants
FAPESP's process: 18/14432-3 - A network for an integrative biology in neglected diseases: bridging epigenetics, metabolism and cell cycle in pathogenic trypanosomatids
Grantee:Ariel Mariano Silber
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 18/15553-9 - Going deeper into Trypanosoma cruzi chromatin regulation: identifying new players and quizzing its impact on a potential transcription control
Grantee:Julia Pinheiro Chagas da Cunha
Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
Grantee:Hugo Aguirre Armelin
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 17/18344-9 - Quantitative chromatin proteomics upon FGF2 treatment: analysis of transcriptional regulation and involvement of cdc42
Grantee:Francisca Nathália de Luna Vitorino
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)