INVESTIGADORES
DE MIGUEL natalia
congresos y reuniones científicas
Título:
Exploring the link between adenine DNA methylation and 3D genome organization in the parasite Trichomonas vaginalis
Autor/es:
LIZARRAGA, AYELEN; STROBL-MAZZULLA, PABLO H.; DE MIGUEL, NATALIA
Reunión:
Congreso; XXXI Reunión Anual. Sociedad Argentina de Protozoología; 2019
Resumen:
Trichomonas vaginalis is a common sexually transmitted parasite thatcolonizes the human urogenital tract causing infections that range fromasymptomatic to highly inflammatory. Chronic infections have been associatedwith high risk pregnancies, increased risk of acquiring HIV and highersusceptibility to developing cervical or prostate cancer. Despite theirimportance in other organisms, the epigenetic mechanisms involved in generegulation in the parasite remain poorly understood. Recent works havehighlighted the importance of histone modifications in the regulation oftranscription and parasite pathogenesis. However, the nature of DNA methylationin the parasite remained unexplored. Using a combination of immunologicaltechniques and UHPLC, we analyzed the abundance of DNA methylation in strainswith differential pathogenicity demonstrating that N6-methyladenine (6mA), andnot 5‐methylcytosine (5mC), is the main DNA methylation mark in T. vaginalis. We performed an adaptedmethylated immunoprecipitation assay followed by high-throughput sequencing(MeDIP-seq) on a patient-derived strain to obtain genome-wide distribution of 6mAmark. Our results revealed that this mark is enriched at intergenic regions,with a preference for certain superfamilies of DNA transposable elements. Weshow that 6mA in T. vaginalis isassociated with silencing when present on genes. Interestingly, bioinformaticsanalysis revealed the presence of transcriptionally active or repressiveintervals flanked by 6mA-enriched regions and results from chromatinconformation capture (3C) experiments suggest these 6mA flanked regions are inclose spatial proximity. These associations were disrupted when parasites weretreated with the demethylation activator ascorbic acid. This finding revealed anew role for 6mA in modulating 3D chromatin structure and gene expression inthis deep-branching eukaryote