Adenine DNA methylation, 3D genome organization and gene expression in the parasite Trichomonas vaginalis

DE MIGUEL, NATALIA

Congreso; Molecular Parasitology Meeting XXXI; 2020

Trichomonas vaginalis is a common sexually transmitted parasitethat colonizes the human urogenital tract causing infections thatrange from asymptomatic to highly inflammatory. Recent workshave highlighted the importance of histone modifications in theregulation of transcription and parasite pathogenesis. However,the nature of DNA methylation in the parasite remains unexplored.Using a combination of immunological techniques and ultrahighperformanceliquid chromatography (UHPLC), we analyzed the abundanceof DNA methylation in strains with differential pathogenicitydemonstrating that N6-methyladenine (6mA), and not 5‐methylcytosine(5mC), is the main DNA methylation mark in T. vaginalis. Genomewidedistribution of 6mA reveals that this mark is enriched atintergenic regions, with a preference for certain superfamilies ofDNA transposable elements. We show that 6mA in T. vaginalis isassociated with silencing when present on genes. Interestingly,bioinformatics analysis revealed the presence of transcriptionallyactive or repressive intervals flanked by 6mA-enriched regions,and results from chromatin conformation capture (3C) experimentssuggest these 6mA flanked regions are in close spatial proximity.These associations were disrupted when parasites were treatedwith the demethylation activator ascorbic acid. This finding revealeda role for 6mA in modulating three-dimensional (3D) chromatin structureand gene expression in this divergent member of the Excavata.