Journal Article

Unravelling the role of epigenetic regulators during embryonic development of Rhipicephalus microplus

Uhl, Marcelle, Galina, Antonio, Rosignoli, Serena, Paiardini, Alessandro, Venancio, Thiago Motta, Mermelstein, Claudia Dos Santos, de Souza, Marcos Paulo Nicolich Camargo, Rotili, Dante, Li Yasumura, Juan Diego de Paula, Vaz Junior, Itabajara da Silva, de Oliveira, Daniel Martins, Parizi, Luis Fernando, Moraes, Bruno, Tirloni, Lucas, Fonseca-Oliveira, Manoel, Arcanjo, Angélica Fernandes, Logullo, Carlos, Amarante, Anderson Mendonça, Fantappié, Marcelo Rosado, Henaut-Jacobs, Sarah, Nunes-da-Fonseca, Rodrigo

2025

Overview

Epigenetic modifications are long-lasting changes to the genome that influence a cell's transcriptional potential, thereby altering its function. These modifications can trigger adaptive responses that impact protein expression and various cellular processes, including differentiation and growth. The primary epigenetic mechanisms identified to date include DNA and RNA methylation, histone modifications, and microRNA-mediated regulation of gene expression. The intricate crosstalk among these mechanisms makes epigenetics a compelling field for the development of novel control strategies, particularly through the use of epigenetic drugs targeting arthropod vectors such as ticks. In this study, we identified the orthologs of canonical histone-modifying enzymes, along with components of the machinery responsible for m C and mA-DNA, and m A-RNA methylations. We further characterized their transcriptional profiles and enzymatic activities during embryonic development. To explore the functional consequences of epigenetic regulation in , we evaluated the effects of various epigenetic inhibitors on the BME26 tick embryonic cell line. Molecular docking simulations were performed to predict the binding mode of these inhibitors to tick enzymes, followed by assessment of their effects on cell viability and morphology. Tick cells exposed to these inhibitors exhibited phenotypic and molecular alterations. Notably, we observed higher levels of DNA methylation in the mitochondrial genome compared to nuclear DNA. Inhibition of DNA methylation using 5'-azacytidine (5'-AZA) was associated with increased activity of the mitochondrial electron transport chain and ATP synthesis, but reduced cellular proliferation. Our findings highlight the importance of epigenetic regulation during tick embryogenesis and suggest that targeting these pathways may offer a novel and promising strategy for tick control.