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Loss of DNMT1o Disrupts Imprinted X Chromosome Inactivation and Accentuates Placental Defects in Females

McGraw, S and Oakes, CC and Martel, J and Cirio, MC and de Zeeuw, P and Mak, W and Plass, C and Bartolomei, MS and Chaillet, JR and Trasler, JM (2013) Loss of DNMT1o Disrupts Imprinted X Chromosome Inactivation and Accentuates Placental Defects in Females. PLoS Genetics, 9 (11). ISSN 1553-7390

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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. 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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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
McGraw, S
Oakes, CC
Martel, J
Cirio, MCmcc19@pitt.eduMCC19
de Zeeuw, P
Mak, W
Plass, C
Bartolomei, MS
Chaillet, JRchaillet@pitt.eduCHAILLET
Trasler, JM
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorLee, Jeannie TUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 November 2013
Date Type: Publication
Journal or Publication Title: PLoS Genetics
Volume: 9
Number: 11
DOI or Unique Handle: 10.1371/journal.pgen.1003873
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
Refereed: Yes
ISSN: 1553-7390
Date Deposited: 30 Jan 2014 18:00
Last Modified: 02 Feb 2019 14:55
URI: http://d-scholarship.pitt.edu/id/eprint/20402

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