Integrating high-throughput analysis to create an atlas of replication origins in Trypanosoma cruzi in the context of genome structure and variability

Autor(es)

Vitarelli, Marcela de Oliveira ; Franco, Thiago Andrade ; Pires, David da Silva ; Lima, Alex Ranieri Jeronimo ; Viala, Vincent Louis ; Kraus, Amelie Johanna ; de Azevedo, Inacio de Loiola Meirelles Junqueira ; da Cunha, Julia Pinheiro Chagas ; Elias, Maria Carolina

• Tipo de documento: Artigo Científico
• Fonte: MBIO; v. 15, n. 4, p. 25-pg., 2024-03-05.

Resumo

Trypanosoma cruzi is the etiologic agent of the most prevalent human parasitic disease in Latin America, Chagas disease. Its genome is rich in multigenic families that code for virulent antigens and are present in the rapidly evolving genomic compartment named Disruptive. DNA replication is a meticulous biological process in which flaws can generate mutations and changes in chromosomal and gene copy numbers. Here, integrating high-throughput and single-molecule analyses, we were able to identify Predominant, Flexible, and Dormant Orc1Cdc6-dependent origins as well as Orc1Cdc6-independent origins. Orc1Cdc6-dependent origins were found in multigenic family loci, while independent origins were found in the Core compartment that contains conserved and hypothetical protein-coding genes, in addition to multigenic families. In addition, we found that Orc1Cdc6 density is related to the firing of origins and that Orc1Cdc6-binding sites within fired origins are depleted of a specific class of nucleosomes that we previously categorized as dynamic. Together, these data suggest that Orc1Cdc6-dependent origins may contribute to the rapid evolution of the Disruptive compartment and, therefore, to the success of T. cruzi infection and that the local epigenome landscape is also involved in this process. (AU)

• Processo FAPESP: 16/50050-2 - How do common and diverged features of the replicative stress response shape the biology of TriTryp parasites?
• Beneficiário: Maria Carolina Quartim Barbosa Elias Sabbaga
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/04483-2 - Dinâmica funcional da proteína Orc1b: análise por ChIP-seq
• Beneficiário: Marcela de Oliveira Vitarelli
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 20/00694-6 - Como o processo de replicação do DNA contribui para o sucesso da infecção causada por Trypanosoma cruzi
• Beneficiário: Maria Carolina Quartim Barbosa Elias Sabbaga
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/07693-2 - Dinâmica funcional da proteína Orc1b durante o ciclo de vida de Trypanosoma
• Beneficiário: Marcela de Oliveira Vitarelli
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 22/01900-4 - Dinâmica da replicação de DNA em Trypanosoma cruzi:consequências do estresse replicativo
• Beneficiário: Thiago Andrade Franco
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado