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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,6,9]]},"abstract":"<jats:p>\n                    <jats:italic>Trichomonas vaginalis<\/jats:italic>\n                    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\u2010methylcytosine (5mC), is the main DNA methylation mark in\n                    <jats:italic>T. vaginalis<\/jats:italic>\n                    . 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\n                    <jats:italic>T. vaginalis<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1917286117","type":"journal-article","created":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T20:06:23Z","timestamp":1590609983000},"page":"13033-13043","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":26,"title":["Adenine DNA methylation, 3D genome organization, and gene expression in the parasite\n                    <i>Trichomonas vaginalis<\/i>"],"prefix":"10.1073","volume":"117","author":[{"given":"Ayelen","family":"Lizarraga","sequence":"first","affiliation":[{"name":"Laboratorio de Par\u00e1sitos Anaerobios, Instituto Tecnol\u00f3gico Chascom\u00fas, National Scientific and Technical Research Council-National University of San Martin (CONICET-UNSAM), B7130IWA Chascom\u00fas, Argentina;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zach Klapholz","family":"O\u2019Brown","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Children\u2019s Hospital Boston, Boston, MA 02115;"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Boulias","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Children\u2019s Hospital Boston, Boston, MA 02115;"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2534-6588","authenticated-orcid":false,"given":"Lara","family":"Roach","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Children\u2019s Hospital Boston, Boston, MA 02115;"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7501-7371","authenticated-orcid":false,"given":"Eric Lieberman","family":"Greer","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Children\u2019s Hospital Boston, Boston, MA 02115;"},{"name":"Department of Pediatrics, Harvard Medical School, Boston, MA 02115;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia J.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology &amp; Molecular Genetics, University of California, Los Angeles, CA 90095;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0591-6168","authenticated-orcid":false,"given":"Pablo H.","family":"Strobl-Mazzulla","sequence":"additional","affiliation":[{"name":"Laboratorio de Biolog\u00eda del Desarrollo, Instituto Tecnol\u00f3gico Chascom\u00fas, CONICET-UNSAM, B7130IWA Chascom\u00fas, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3864-0703","authenticated-orcid":false,"given":"Natalia","family":"de Miguel","sequence":"additional","affiliation":[{"name":"Laboratorio de Par\u00e1sitos Anaerobios, Instituto Tecnol\u00f3gico Chascom\u00fas, National Scientific and Technical Research Council-National University of San Martin (CONICET-UNSAM), B7130IWA Chascom\u00fas, Argentina;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,5,27]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1186\/s12879-015-1055-0","article-title":"Trichomonas vaginalis: A review of epidemiologic, clinical and treatment issues","volume":"15","author":"Kissinger P.","year":"2015","unstructured":"P. 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