Artículo
Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females.
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.
Fecha de publicación:
21/11/2013
Editorial:
Public Library Science
Revista:
Plos Genetics
ISSN:
1553-7390
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
Methylation
,
Dna
,
Imprinting
,
Embryos
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Articulos(IFIBYNE)
Articulos de INST.DE FISIOL., BIOL.MOLECULAR Y NEUROCIENCIAS
Articulos de INST.DE FISIOL., BIOL.MOLECULAR Y NEUROCIENCIAS
Articulos(OCA CIUDAD UNIVERSITARIA)
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA CIUDAD UNIVERSITARIA
Articulos de OFICINA DE COORDINACION ADMINISTRATIVA CIUDAD UNIVERSITARIA
Citación
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;
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