Artículo
Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis
Lizarraga, Ayelen
; O'Brown, Zach Klapholz; Boulias, Konstantinos; Roach, Lara; Greer, Eric Lieberman; Johnson, Patricia J.; Strobl Mazzulla, Pablo H.; de Miguel, Natalia
![Icon](/themes/CONICETDigital/images/conicet.png)
![Icon](/themes/CONICETDigital/images/conicet.png)
Fecha de publicación:
06/2020
Editorial:
National Academy of Sciences
Revista:
Proceedings of the National Academy of Sciences of The United States of America
ISSN:
0027-8424
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Trichomonas vaginalis is a common sexually transmitted parasite that colonizes the human urogenital tract causing infections that range from asymptomatic to highly inflammatory. Recent works have highlighted the importance of histone modifications in the regulation of transcription and parasite pathogenesis. However, the nature of DNA methylation in the parasite remains unexplored. Using a combination of immunological techniques and ultrahigh-performance liquid chromatography (UHPLC), we analyzed the abundance of DNA methylation in strains with differential pathogenicity demonstrating that N6-methyladenine (6mA), and not 5‐methylcytosine (5mC), is the main DNA methylation mark in T. vaginalis. Genome-wide distribution of 6mA reveals that this mark is enriched at intergenic regions, with a preference for certain superfamilies of DNA transposable elements. We show that 6mA in T. vaginalis is associated with silencing when present on genes. Interestingly, bioinformatics analysis revealed the presence of transcriptionally active or repressive intervals flanked by 6mA-enriched regions, and results from chromatin conformation capture (3C) experiments suggest these 6mA flanked regions are in close spatial proximity. These associations were disrupted when parasites were treated with the demethylation activator ascorbic acid. This finding revealed a role for 6mA in modulating three-dimensional (3D) chromatin structure and gene expression in this divergent member of the Excavata.
Palabras clave:
ADENINE METHYLATION
,
GENE EXPRESSION
,
TRICHOMONAS
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Identificadores
Colecciones
Articulos(CCT - LA PLATA)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - LA PLATA
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - LA PLATA
Citación
Lizarraga, Ayelen; O'Brown, Zach Klapholz; Boulias, Konstantinos; Roach, Lara; Greer, Eric Lieberman; et al.; Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 117; 23; 6-2020; 13033-13043
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