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Loss of DNMT1o Disrupts Imprinted X Chromosome Inactivation and Accentuates Placental Defects in Females
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نویسنده
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mcgraw s. ,oakes c.c. ,martel j. ,cirio m.c. ,de zeeuw p. ,mak w. ,plass c. ,bartolomei m.s. ,chaillet j.r. ,trasler j.m.
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منبع
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plos genetics - 2013 - دوره : 9 - شماره : 11
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چکیده
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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. dnmt1omat-/- mouse embryos born to dnmt1δ1o/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 dnmt1δ1o/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. © 2013 mcgraw et al.
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آدرس
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departments of pharmacology and therapeutics,pediatrics and human genetics,research institute at the montreal children's hospital of the mcgill university health centre,mcgill university,montreal,qc, Canada, department of epigenomics and cancer risk factors,the german cancer research center,heidelberg,baden-württemberg, Germany, departments of pharmacology and therapeutics,pediatrics and human genetics,research institute at the montreal children's hospital of the mcgill university health centre,mcgill university,montreal,qc, Canada, department of microbiology and molecular genetics,university of pittsburgh,pittsburgh,pa, United States, departments of pharmacology and therapeutics,pediatrics and human genetics,research institute at the montreal children's hospital of the mcgill university health centre,mcgill university,montreal,qc, Canada, department of cell and developmental biology,university of pennsylvania perelman school of medicine,philadelphia,pa, United States, department of epigenomics and cancer risk factors,the german cancer research center,heidelberg,baden-württemberg, Germany, department of cell and developmental biology,university of pennsylvania perelman school of medicine,philadelphia,pa, United States, department of microbiology and molecular genetics,university of pittsburgh,pittsburgh,pa, United States, departments of pharmacology and therapeutics,pediatrics and human genetics,research institute at the montreal children's hospital of the mcgill university health centre,mcgill university,montreal,qc, Canada
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Authors
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