Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females.

Autores
Mcgraw, Serge; Oakes, Christopher C.; Martel, Josée; Cirio, Maria Cecilia; de Zeeuw, Pauline; Mak, Winifred; Pass, Christoph; Bartolomei, Marisa S.; Chaillet, J. Richard; Trasler, Jaquetta M.
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The maintenance of key germline derived DNA methylation patterns during preimplantation development depends on stores of DNA cytosine methyltransferase-1o (DNMT1o) provided by the oocyte. Dnmt1o(mat-/-) mouse embryos born to Dnmt1(Δ1o/Δ1o) female mice lack DNMT1o protein and have disrupted genomic imprinting and associated phenotypic abnormalities. Here, we describe additional female-specific morphological abnormalities and DNA hypomethylation defects outside imprinted loci, restricted to extraembryonic tissue. Compared to male offspring, the placentae of female offspring of Dnmt1(Δ1o/Δ1o) mothers displayed a higher incidence of genic and intergenic hypomethylation and more frequent and extreme placental dysmorphology. The majority of the affected loci were concentrated on the X chromosome and associated with aberrant biallelic expression, indicating that imprinted X-inactivation was perturbed. Hypomethylation of a key regulatory region of Xite within the X-inactivation center was present in female blastocysts shortly after the absence of methylation maintenance by DNMT1o at the 8-cell stage. The female preponderance of placental DNA hypomethylation associated with maternal DNMT1o deficiency provides evidence of additional roles beyond the maintenance of genomic imprints for DNA methylation events in the preimplantation embryo, including a role in imprinted X chromosome inactivation.
Fil: Mcgraw, Serge.
Fil: Oakes, Christopher C..
Fil: Martel, Josée.
Fil: Cirio, Maria Cecilia.
Fil: de Zeeuw, Pauline.
Fil: Mak, Winifred.
Fil: Pass, Christoph.
Fil: Bartolomei, Marisa S..
Fil: Chaillet, J. Richard.
Fil: Trasler, Jaquetta M..
Materia
methylation
DNA
imprinting
embryos
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:11336/583
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/583
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females.Mcgraw, SergeOakes, Christopher C.Martel, JoséeCirio, Maria Ceciliade Zeeuw, PaulineMak, WinifredPass, ChristophBartolomei, Marisa S.Chaillet, J. RichardTrasler, Jaquetta M.methylationDNAimprintingembryoshttps://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6The maintenance of key germline derived DNA methylation patterns during preimplantation development depends on stores of DNA cytosine methyltransferase-1o (DNMT1o) provided by the oocyte. Dnmt1o(mat-/-) mouse embryos born to Dnmt1(Δ1o/Δ1o) female mice lack DNMT1o protein and have disrupted genomic imprinting and associated phenotypic abnormalities. Here, we describe additional female-specific morphological abnormalities and DNA hypomethylation defects outside imprinted loci, restricted to extraembryonic tissue. Compared to male offspring, the placentae of female offspring of Dnmt1(Δ1o/Δ1o) mothers displayed a higher incidence of genic and intergenic hypomethylation and more frequent and extreme placental dysmorphology. The majority of the affected loci were concentrated on the X chromosome and associated with aberrant biallelic expression, indicating that imprinted X-inactivation was perturbed. Hypomethylation of a key regulatory region of Xite within the X-inactivation center was present in female blastocysts shortly after the absence of methylation maintenance by DNMT1o at the 8-cell stage. The female preponderance of placental DNA hypomethylation associated with maternal DNMT1o deficiency provides evidence of additional roles beyond the maintenance of genomic imprints for DNA methylation events in the preimplantation embryo, including a role in imprinted X chromosome inactivation.Fil: Mcgraw, Serge.Fil: Oakes, Christopher C..Fil: Martel, Josée.Fil: Cirio, Maria Cecilia.Fil: de Zeeuw, Pauline.Fil: Mak, Winifred.Fil: Pass, Christoph.Fil: Bartolomei, Marisa S..Fil: Chaillet, J. Richard.Fil: Trasler, Jaquetta M..Public Library Science2013-11-21info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/583Mcgraw, Serge; Oakes, Christopher C.; Martel, Josée; Cirio, Maria Cecilia; de Zeeuw, Pauline; Mak, Winifred; Pass, Christoph; Bartolomei, Marisa S.; Chaillet, J. Richard; Trasler, Jaquetta M. ; Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females.; Public Library Science; Plos Genetics; 9; 11; 21-11-2013; 1-15;1553-7390enginfo:eu-repo/semantics/altIdentifier/doi/ 10.1371/journal.pgen.1003873info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-12T09:57:49Zoai:ri.conicet.gov.ar:11336/583instacron: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:34982025-11-12 09:57:49.54CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females.
title Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females.
spellingShingle Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females.
Mcgraw, Serge
methylation
DNA
imprinting
embryos
title_short Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females.
title_full Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females.
title_fullStr Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females.
title_full_unstemmed Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females.
title_sort Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females.
dc.creator.none.fl_str_mv Mcgraw, Serge
Oakes, Christopher C.
Martel, Josée
Cirio, Maria Cecilia
de Zeeuw, Pauline
Mak, Winifred
Pass, Christoph
Bartolomei, Marisa S.
Chaillet, J. Richard
Trasler, Jaquetta M.
author Mcgraw, Serge
author_facet Mcgraw, Serge
Oakes, Christopher C.
Martel, Josée
Cirio, Maria Cecilia
de Zeeuw, Pauline
Mak, Winifred
Pass, Christoph
Bartolomei, Marisa S.
Chaillet, J. Richard
Trasler, Jaquetta M.
author_role author
author2 Oakes, Christopher C.
Martel, Josée
Cirio, Maria Cecilia
de Zeeuw, Pauline
Mak, Winifred
Pass, Christoph
Bartolomei, Marisa S.
Chaillet, J. Richard
Trasler, Jaquetta M.
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv methylation
DNA
imprinting
embryos
topic methylation
DNA
imprinting
embryos
purl_subject.fl_str_mv https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
dc.description.none.fl_txt_mv The maintenance of key germline derived DNA methylation patterns during preimplantation development depends on stores of DNA cytosine methyltransferase-1o (DNMT1o) provided by the oocyte. Dnmt1o(mat-/-) mouse embryos born to Dnmt1(Δ1o/Δ1o) female mice lack DNMT1o protein and have disrupted genomic imprinting and associated phenotypic abnormalities. Here, we describe additional female-specific morphological abnormalities and DNA hypomethylation defects outside imprinted loci, restricted to extraembryonic tissue. Compared to male offspring, the placentae of female offspring of Dnmt1(Δ1o/Δ1o) mothers displayed a higher incidence of genic and intergenic hypomethylation and more frequent and extreme placental dysmorphology. The majority of the affected loci were concentrated on the X chromosome and associated with aberrant biallelic expression, indicating that imprinted X-inactivation was perturbed. Hypomethylation of a key regulatory region of Xite within the X-inactivation center was present in female blastocysts shortly after the absence of methylation maintenance by DNMT1o at the 8-cell stage. The female preponderance of placental DNA hypomethylation associated with maternal DNMT1o deficiency provides evidence of additional roles beyond the maintenance of genomic imprints for DNA methylation events in the preimplantation embryo, including a role in imprinted X chromosome inactivation.
Fil: Mcgraw, Serge.
Fil: Oakes, Christopher C..
Fil: Martel, Josée.
Fil: Cirio, Maria Cecilia.
Fil: de Zeeuw, Pauline.
Fil: Mak, Winifred.
Fil: Pass, Christoph.
Fil: Bartolomei, Marisa S..
Fil: Chaillet, J. Richard.
Fil: Trasler, Jaquetta M..
description The maintenance of key germline derived DNA methylation patterns during preimplantation development depends on stores of DNA cytosine methyltransferase-1o (DNMT1o) provided by the oocyte. Dnmt1o(mat-/-) mouse embryos born to Dnmt1(Δ1o/Δ1o) female mice lack DNMT1o protein and have disrupted genomic imprinting and associated phenotypic abnormalities. Here, we describe additional female-specific morphological abnormalities and DNA hypomethylation defects outside imprinted loci, restricted to extraembryonic tissue. Compared to male offspring, the placentae of female offspring of Dnmt1(Δ1o/Δ1o) mothers displayed a higher incidence of genic and intergenic hypomethylation and more frequent and extreme placental dysmorphology. The majority of the affected loci were concentrated on the X chromosome and associated with aberrant biallelic expression, indicating that imprinted X-inactivation was perturbed. Hypomethylation of a key regulatory region of Xite within the X-inactivation center was present in female blastocysts shortly after the absence of methylation maintenance by DNMT1o at the 8-cell stage. The female preponderance of placental DNA hypomethylation associated with maternal DNMT1o deficiency provides evidence of additional roles beyond the maintenance of genomic imprints for DNA methylation events in the preimplantation embryo, including a role in imprinted X chromosome inactivation.
publishDate 2013
dc.date.none.fl_str_mv 2013-11-21
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/11336/583
Mcgraw, Serge; Oakes, Christopher C.; Martel, Josée; Cirio, Maria Cecilia; de Zeeuw, Pauline; Mak, Winifred; Pass, Christoph; Bartolomei, Marisa S.; Chaillet, J. Richard; Trasler, Jaquetta M. ; Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females.; Public Library Science; Plos Genetics; 9; 11; 21-11-2013; 1-15;
1553-7390
url http://hdl.handle.net/11336/583
identifier_str_mv Mcgraw, Serge; Oakes, Christopher C.; Martel, Josée; Cirio, Maria Cecilia; de Zeeuw, Pauline; Mak, Winifred; Pass, Christoph; Bartolomei, Marisa S.; Chaillet, J. Richard; Trasler, Jaquetta M. ; Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females.; Public Library Science; Plos Genetics; 9; 11; 21-11-2013; 1-15;
1553-7390
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/ 10.1371/journal.pgen.1003873
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 Public Library Science
publisher.none.fl_str_mv Public Library Science
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
_version_ 1848598385346478080
score 13.25334

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