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dc.contributor.author
Mcgraw, Serge
dc.contributor.author
Oakes, Christopher C.
dc.contributor.author
Martel, Josée
dc.contributor.author
Cirio, Maria Cecilia
dc.contributor.author
de Zeeuw, Pauline
dc.contributor.author
Mak, Winifred
dc.contributor.author
Pass, Christoph
dc.contributor.author
Bartolomei, Marisa S.
dc.contributor.author
Chaillet, J. Richard
dc.contributor.author
Trasler, Jaquetta M.
dc.date.available
2015-05-27T18:18:03Z
dc.date.issued
2013-11-21
dc.identifier.citation
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;
dc.identifier.issn
1553-7390
dc.identifier.uri
http://hdl.handle.net/11336/583
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Public Library Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Methylation
dc.subject
Dna
dc.subject
Imprinting
dc.subject
Embryos
dc.subject.classification
Ciencias Naturales y Exactas
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
Biología Reproductiva (aspectos Médicos Van En 3 "ciencias Médicas y de la Hídrico Salud")
dc.title
Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females.
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-03-30 10:35:44.97925-03
dc.journal.volume
9
dc.journal.number
11
dc.journal.pagination
1-15
dc.journal.pais
Estados Unidos
dc.journal.ciudad
San Francisco
dc.description.fil
Fil: Mcgraw, Serge.
dc.description.fil
Fil: Oakes, Christopher C..
dc.description.fil
Fil: Martel, Josée.
dc.description.fil
Fil: Cirio, Maria Cecilia.
dc.description.fil
Fil: de Zeeuw, Pauline.
dc.description.fil
Fil: Mak, Winifred.
dc.description.fil
Fil: Pass, Christoph.
dc.description.fil
Fil: Bartolomei, Marisa S..
dc.description.fil
Fil: Chaillet, J. Richard.
dc.description.fil
Fil: Trasler, Jaquetta M..
dc.journal.title
Plos Genetics
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/ 10.1371/journal.pgen.1003873
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