Authors

A Lima²; S Poubel²; J Roson²; L de Lima²; H Costa-Silva²; HG Silva²; PC de Lima²; CS gonçalves²; PA Galante⁶; FB Holetz⁴; MC Motta³; AM Silber¹; MC Elias²; JP Cunha⁵;  ¹ Biomedical Science Institute - USP, Brazil;  ² INSTITUTO BUTANTAN, CELL CYCLE SPECIAL LAB, SÃO PAULO, Brazil;  ³ Laboratorio de Ultraestrutura Celular Hertha Meyer, Instituto de Biofısica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil;  ⁴ Laboratório de Regulação da Expressão Gênica, Instituto Carlos Chagas, Fiocruz, Brazil;  ⁵ BUTANTAN, Brazil;  ⁶ Hospital Sirio Libanes, Brazil

Discussion

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.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 genome-wide approaches supported by transmission electron microscopy. The integration of FAIRE and MNase-seq data, two complementary epigenomic approaches, enabled us to identify differences in T. cruzi genome compartments, putative transcriptional start regions, and virulence factors. In addition, we also detected developmental chromatin regulation at tRNA loci (tDNA), which seems to be linked to the translation regulatory mechanism required for parasite differentiation. Strikingly, a positive correlation was observed between active chromatin and steady-state and nascent transcription levels. 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. Supported by FAPESP, Serrapilheira, CAPES.