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

Epigenetics Chromatin. 2022 Jun 1;15(1):22. doi: 10.1186/s13072-022-00450-x.

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.

Keywords: Active chromatin; Cell differentiation; Chromatin remodeling; Epigenomics; FAIRE-seq; Gene expression control; Polycistronic transcription; Trypanosoma cruzi; Virulence factors; tRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin Assembly and Disassembly
  • Chromatin* / genetics
  • Chromatin* / metabolism
  • Gene Expression Regulation
  • Proteomics / methods
  • Trypanosoma cruzi* / genetics
  • Trypanosoma cruzi* / metabolism

Substances

  • Chromatin