Open chromatin analysis in Trypanosoma cruzi life forms highlights critical differences in genomic compartments and developmental regulation at tDNA loci

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Jeronimo Lima, Alex Ranieri ; de Sousa Silva, Herbert Guimaraes ; Poubel, Saloe ; Roson, Juliana Nunes ; Oliveira de Lima, Loyze Paola ; Costa-Silva, Hellida Marina ; Goncalves, Camila Silva ; Galante, Pedro A. F. ; Holetz, Fabiola ; Motta, Maria Cristina Machado M. ; Silber, Ariel M. ; Elias, M. Carolina ; Chagas da Cunha, Julia Pinheiro

• Document type: Journal article
• Source: EPIGENETICS & CHROMATIN; v. 15, n. 1, p. 16-pg., 2022-06-01.

Abstract

Background Genomic organization and gene expression regulation in trypanosomes are remarkable because protein-coding genes are organized into codirectional gene clusters with unrelated functions. Moreover, there is no dedicated promoter for each gene, resulting in polycistronic gene transcription, with posttranscriptional control playing a major role. Nonetheless, these parasites harbor epigenetic modifications at critical regulatory genome features that dynamically change among parasite stages, which are not fully understood. Results Here, we investigated the impact of chromatin changes in a scenario commanded by posttranscriptional control exploring the parasite Trypanosoma cruzi and its differentiation program using FAIRE-seq approach supported by transmission electron microscopy. We identified differences in T. cruzi genome compartments, putative transcriptional start regions, and virulence factors. In addition, we also detected a developmental chromatin regulation at tRNA loci (tDNA), which could be linked to the intense chromatin remodeling and/or the translation regulatory mechanism required for parasite differentiation. We further integrated the open chromatin profile with public transcriptomic and MNase-seq datasets. Strikingly, a positive correlation was observed between active chromatin and steady-state transcription levels. Conclusion Taken together, our results indicate that chromatin changes reflect the unusual gene expression regulation of trypanosomes and the differences among parasite developmental stages, even in the context of a lack of canonical transcriptional control of protein-coding genes. (AU)

• 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: 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: 20/02708-4 - Exploring the role of chromatin-associated proteins detected in Trypanosoma cruzi
• Grantee: Herbert Guimarães de Sousa Silva
• Support Opportunities: Scholarships in Brazil - Master
• 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: 19/19834-5 - Describing new players at Trypanosoma cruzi chromatin by locus-specific chromatin immunoprecipitation
• Grantee: Hellida Marina Costa Silva
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/19690-3 - Genome-wide approaches to reveal epigenomic structure in trypanosomes subjected to metabolic states changes and during cell cycle
• Grantee: Alex Ranieri Jerônimo Lima
• Support Opportunities: Scholarships in Brazil - Post-Doctoral