Epigenetic Regulates Transcription and Pathogenesis in the Parasite Trichomonas Vaginalis.
Pachano, T., Nievas, Y. R., Lizarraga, A., Johnson, P. J., Strobl-Mazzulla, P. H. and de Miguel, N.
Laboratorio de Parasitos Anaerobios, Instituto de Investigaciones Biotecnologicas-Instituto Tecnologico Chascomus (IIB-INTECH), CONICET-UNSAM, Chascomus, B7130IWA, Argentina.
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, California, 90095-1489, USA.
Laboratorio de Biologia del Desarrollo, Instituto de Investigaciones Biotecnologicas-Instituto Tecnologico Chascomus (IIB-INTECH), CONICET-UNSAM, Chascomus, B7130IWA, Argentina.
Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract. Infections range from asymptomatic to highly inflammatory, depending on the host and the parasite strain. Different T. vaginalis strains vary greatly in their adherence and cytolysis capacities. These phenotypic differences might be attributed to differentially expressed genes as a consequence of extra-genetic variation, such as epigenetic modifications. In this study we explored the role of histone acetylation in regulating gene transcription and pathogenesis in T. vaginalis. Here, we show that histone 3 lysine acetylation (H3KAc) is enriched in nucleosomes positioned around the transcription start site of active genes (BAP1 and BAP2) in a highly-adherent parasite strain; compared with the low acetylation abundance in contrast to that observed in a less-adherent strain that expresses these genes at low levels. Additionally, exposition of less-adherent strain with a specific histone deacetylases inhibitor, trichostatin A (TSA), upregulated the transcription of BAP1 and BAP2 genes in concomitance with an increase in H3KAc abundance and chromatin accessibility around their transcription start sites. Moreover, we demonstrated that the binding of IBP39, the transcription factor responsible for the initiation of transcription of ~75% of known T. vaginalis genes, depends on the histone acetylation state around the metazoan-like initiator (Inr) to which IBP39 binds. Finally, we found that TSA treatment increased parasite aggregation and adherence to host cells. Our data demonstrated for the first time that H3KAc is a permissive histone modification that functions to mediate both transcription and pathogenesis of the parasite T. vaginalis. This article is protected by copyright. All rights reserved.
Cellular Microbiology 19(6): en prensa (2017)