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Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis.
Proc Natl Acad Sci U S A. 2020 06 09; 117(23):13033-13043.PN

Abstract

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.

Authors+Show Affiliations

Laboratorio de Parásitos Anaerobios, Instituto Tecnológico Chascomús, National Scientific and Technical Research Council-National University of San Martin (CONICET-UNSAM), B7130IWA Chascomús, Argentina.Division of Newborn Medicine, Children's Hospital Boston, Boston, MA 02115. Department of Pediatrics, Harvard Medical School, Boston, MA 02115.Division of Newborn Medicine, Children's Hospital Boston, Boston, MA 02115. Department of Pediatrics, Harvard Medical School, Boston, MA 02115.Division of Newborn Medicine, Children's Hospital Boston, Boston, MA 02115. Department of Pediatrics, Harvard Medical School, Boston, MA 02115.Division of Newborn Medicine, Children's Hospital Boston, Boston, MA 02115. Department of Pediatrics, Harvard Medical School, Boston, MA 02115.Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095; johnsonp@ucla.edu ndemiguel@intech.gov.ar.Laboratorio de Biología del Desarrollo, Instituto Tecnológico Chascomús, CONICET-UNSAM, B7130IWA Chascomús, Argentina.Laboratorio de Parásitos Anaerobios, Instituto Tecnológico Chascomús, National Scientific and Technical Research Council-National University of San Martin (CONICET-UNSAM), B7130IWA Chascomús, Argentina; johnsonp@ucla.edu ndemiguel@intech.gov.ar.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32461362

Citation

Lizarraga, Ayelen, et al. "Adenine DNA Methylation, 3D Genome Organization, and Gene Expression in the Parasite Trichomonas Vaginalis." Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 23, 2020, pp. 13033-13043.
Lizarraga A, O'Brown ZK, Boulias K, et al. Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis. Proc Natl Acad Sci USA. 2020;117(23):13033-13043.
Lizarraga, A., O'Brown, Z. K., Boulias, K., Roach, L., Greer, E. L., Johnson, P. J., Strobl-Mazzulla, P. H., & de Miguel, N. (2020). Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis. Proceedings of the National Academy of Sciences of the United States of America, 117(23), 13033-13043. https://doi.org/10.1073/pnas.1917286117
Lizarraga A, et al. Adenine DNA Methylation, 3D Genome Organization, and Gene Expression in the Parasite Trichomonas Vaginalis. Proc Natl Acad Sci USA. 2020 06 9;117(23):13033-13043. PubMed PMID: 32461362.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis. AU - Lizarraga,Ayelen, AU - O'Brown,Zach Klapholz, AU - Boulias,Konstantinos, AU - Roach,Lara, AU - Greer,Eric Lieberman, AU - Johnson,Patricia J, AU - Strobl-Mazzulla,Pablo H, AU - de Miguel,Natalia, Y1 - 2020/05/27/ PY - 2020/11/27/pmc-release PY - 2020/5/29/pubmed PY - 2020/5/29/medline PY - 2020/5/29/entrez KW - Trichomonas KW - adenine methylation KW - gene expression SP - 13033 EP - 13043 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 117 IS - 23 N2 - 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. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/32461362/Adenine_DNA_methylation,_3D_genome_organization,_and_gene_expression_in_the_parasite_Trichomonas_vaginalis L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=32461362 DB - PRIME DP - Unbound Medicine ER -
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