Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis

Autores
Lizarraga, Ayelen; O'Brown, Zach Klapholz; Boulias, Konstantinos; Roach, Lara; Greer, Eric Lieberman; Johnson, Patricia J.; Strobl Mazzulla, Pablo H.; de Miguel, Natalia
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
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
Fil: O'Brown, Zach Klapholz. Harvard Medical School; Estados Unidos
Fil: Boulias, Konstantinos. Harvard Medical School; Estados Unidos
Fil: Roach, Lara. Harvard Medical School; Estados Unidos
Fil: Greer, Eric Lieberman. Harvard Medical School; Estados Unidos
Fil: Johnson, Patricia J.. University of California at Los Angeles; Estados Unidos
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
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
Materia
ADENINE METHYLATION
GENE EXPRESSION
TRICHOMONAS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/133338
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/133338
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalisLizarraga, AyelenO'Brown, Zach KlapholzBoulias, KonstantinosRoach, LaraGreer, Eric LiebermanJohnson, Patricia J.Strobl Mazzulla, Pablo H.de Miguel, NataliaADENINE METHYLATIONGENE EXPRESSIONTRICHOMONAShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Trichomonas 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.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.; ArgentinaFil: O'Brown, Zach Klapholz. Harvard Medical School; Estados UnidosFil: Boulias, Konstantinos. Harvard Medical School; Estados UnidosFil: Roach, Lara. Harvard Medical School; Estados UnidosFil: Greer, Eric Lieberman. Harvard Medical School; Estados UnidosFil: Johnson, Patricia J.. University of California at Los Angeles; Estados UnidosFil: 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.; ArgentinaFil: 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.; ArgentinaNational Academy of Sciences2020-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/133338Lizarraga, 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; 13033-130430027-8424CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1917286117info:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/content/117/23/13033info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:15Zoai:ri.conicet.gov.ar:11336/133338instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:44:15.644CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis
title Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis
spellingShingle Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis
Lizarraga, Ayelen
ADENINE METHYLATION
GENE EXPRESSION
TRICHOMONAS
title_short Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis
title_full Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis
title_fullStr Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis
title_full_unstemmed Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis
title_sort Adenine DNA methylation, 3D genome organization, and gene expression in the parasite Trichomonas vaginalis
dc.creator.none.fl_str_mv Lizarraga, Ayelen
O'Brown, Zach Klapholz
Boulias, Konstantinos
Roach, Lara
Greer, Eric Lieberman
Johnson, Patricia J.
Strobl Mazzulla, Pablo H.
de Miguel, Natalia
author Lizarraga, Ayelen
author_facet Lizarraga, Ayelen
O'Brown, Zach Klapholz
Boulias, Konstantinos
Roach, Lara
Greer, Eric Lieberman
Johnson, Patricia J.
Strobl Mazzulla, Pablo H.
de Miguel, Natalia
author_role author
author2 O'Brown, Zach Klapholz
Boulias, Konstantinos
Roach, Lara
Greer, Eric Lieberman
Johnson, Patricia J.
Strobl Mazzulla, Pablo H.
de Miguel, Natalia
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ADENINE METHYLATION
GENE EXPRESSION
TRICHOMONAS
topic ADENINE METHYLATION
GENE EXPRESSION
TRICHOMONAS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
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
Fil: O'Brown, Zach Klapholz. Harvard Medical School; Estados Unidos
Fil: Boulias, Konstantinos. Harvard Medical School; Estados Unidos
Fil: Roach, Lara. Harvard Medical School; Estados Unidos
Fil: Greer, Eric Lieberman. Harvard Medical School; Estados Unidos
Fil: Johnson, Patricia J.. University of California at Los Angeles; Estados Unidos
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
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
description 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.
publishDate 2020
dc.date.none.fl_str_mv 2020-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/133338
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
0027-8424
CONICET Digital
CONICET
url http://hdl.handle.net/11336/133338
identifier_str_mv 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
0027-8424
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1917286117
info:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/content/117/23/13033
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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