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dc.contributor.author
Lizarraga, Ayelen
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dc.contributor.author
O'Brown, Zach Klapholz
dc.contributor.author
Boulias, Konstantinos
dc.contributor.author
Roach, Lara
dc.contributor.author
Greer, Eric Lieberman
dc.contributor.author
Johnson, Patricia J.
dc.contributor.author
Strobl Mazzulla, Pablo H.
dc.contributor.author
de Miguel, Natalia
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dc.date.available
2021-06-07T15:14:52Z
dc.date.issued
2020-06
dc.identifier.citation
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
dc.identifier.issn
0027-8424
dc.identifier.uri
http://hdl.handle.net/11336/133338
dc.description.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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
National Academy of Sciences
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
ADENINE METHYLATION
dc.subject
GENE EXPRESSION
dc.subject
TRICHOMONAS
dc.subject.classification
Bioquímica y Biología Molecular
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dc.subject.classification
Ciencias Biológicas
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dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
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dc.title
Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2021-06-04T17:06:31Z
dc.journal.volume
117
dc.journal.number
23
dc.journal.pagination
13033-13043
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
Washington
dc.description.fil
Fil: Lizarraga, Ayelen. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
dc.description.fil
Fil: O'Brown, Zach Klapholz. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Boulias, Konstantinos. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Roach, Lara. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Greer, Eric Lieberman. Harvard Medical School; Estados Unidos
dc.description.fil
Fil: Johnson, Patricia J.. University of California at Los Angeles; Estados Unidos
dc.description.fil
Fil: Strobl Mazzulla, Pablo H.. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
dc.description.fil
Fil: de Miguel, Natalia. Universidad Nacional de San Martin. Instituto Tecnologico de Chascomus. - Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - la Plata. Instituto Tecnologico de Chascomus.; Argentina
dc.journal.title
Proceedings of the National Academy of Sciences of The United States of America
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1073/pnas.1917286117
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/content/117/23/13033
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