| Full text | |
| Author(s): |
Lima, Alex R. J.
[1, 2]
;
de Araujo, Christiane B.
[1, 2]
;
Bispo, Saloe
[1, 2]
;
Patane, Jose
[1, 2]
;
Silber, Ariel M.
[3]
;
Elias, M. Carolina
[1, 2]
;
da Cunha, Julia P. C.
[1, 2]
Total Authors: 7
|
| Affiliation: | [1] Inst Butantan, Ctr Toxins Immune Response & Cell Signaling CeTIC, Sao Paulo - Brazil
[2] Inst Butantan, Lab Ciclo Celular, Sao Paulo - Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Lab Biochem Tryps LaBTryps, Sao Paulo - Brazil
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | PLOS PATHOGENS; v. 17, n. 1 JAN 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
Trypanosoma cruzi alternates between replicative and nonreplicative life forms, accompanied by a shift in global transcription levels and by changes in the nuclear architecture, the chromatin proteome and histone posttranslational modifications. To gain further insights into the epigenetic regulation that accompanies life form changes, we performed genome-wide high-resolution nucleosome mapping using two T. cruzi life forms (epimastigotes and cellular trypomastigotes). By combining a powerful pipeline that allowed us to faithfully compare nucleosome positioning and occupancy, more than 125 thousand nucleosomes were mapped, and approximately 20% of them differed between replicative and nonreplicative forms. The nonreplicative forms have less dynamic nucleosomes, possibly reflecting their lower global transcription levels and DNA replication arrest. However, dynamic nucleosomes are enriched at nonreplicative regulatory transcription initiation regions and at multigenic family members, which are associated with infective-stage and virulence factors. Strikingly, dynamic nucleosome regions are associated with GO terms related to nuclear division, translation, gene regulation and metabolism and, notably, associated with transcripts with different expression levels among life forms. Finally, the nucleosome landscape reflects the steady-state transcription expression: more abundant genes have a more deeply nucleosome-depleted region at putative 5' splice sites, likely associated with trans-splicing efficiency. Taken together, our results indicate that chromatin architecture, defined primarily by nucleosome positioning and occupancy, reflects the phenotypic differences found among T. cruzi life forms despite the lack of a canonical transcriptional control context. Author summary Trypanosomes have profound changes in their morphology and gene expression along life forms, with clear changes on expression of virulence factors, on transcriptional activity and on proliferation capacity. How all these processes are achieved remains unsolved especially considering that, in these organisms, gene regulation relies mainly on posttranscriptional mechanisms. Here, we show that chromatin organization, held primarily on nucleosome positioning and occupancy, differs at strategic genomic regions and reflects phenotypic differences observed among T. cruzi life forms. The putative transcription starts sites and multigenic family members -that code for virulence factors, are differentially enriched on dynamic nucleosomes among replicative and nonreplicative T. cruzi forms. In addition to that, genes associated with DNA replication, cytokinesis, transcription and translation regulation are mainly enriched on dynamic nucleosomes. (AU) | |
| 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: | 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 |
| 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: | 16/50050-2 - How do common and diverged features of the replicative stress response shape the biology of TriTryp parasites? |
| Grantee: | Maria Carolina Quartim Barbosa Elias Sabbaga |
| Support Opportunities: | Research Projects - Thematic Grants |
| 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 |