Protection against de novo methylation is instrumental in maintaining parent-of-origin methylation inherited from the gametes.
Identifying loci with parental differences in DNA methylation is key to unraveling parent-of-origin phenotypes. By conducting a MeDIP-Seq screen in maternal-methylation free postimplantation mouse embryos (Dnmt3L-/+), we demonstrate that maternal-specific methylation exists very scarcely at midgestation. We reveal two forms of oocyte-specific methylation inheritance: limited to preimplantation, or with longer duration, i.e. maternally imprinted loci. Transient and imprinted maternal germline DMRs (gDMRs) are indistinguishable in gametes and preimplantation embryos, however, de novo methylation of paternal alleles at implantation delineates their fates and acts as a major leveling factor of parent-inherited differences. We characterize two new imprinted gDMRs, at the Cdh15 and AK008011 loci, with tissue-specific imprinting loss, again by paternal methylation gain. Protection against demethylation after fertilization has been emphasized as instrumental in maintaining parent-of-origin methylation inherited from the gametes. Here we provide evidence that protection against de novo methylation acts as an equal major pivot, at implantation and throughout life.
INSERM U934/CNRS UMR3215, Institut Curie, 75248 Paris Cedex 05, France.
Charlotte
C
Proudhon
Rachel
R
Duffié
Sophie
S
Ajjan
Michael
M
Cowley
Julian
J
Iranzo
Guillermo
G
Carbajosa
Heba
H
Saadeh
Michelle L
ML
Holland
Rebecca J
RJ
Oakey
Vardhman K
VK
Rakyan
Reiner
R
Schulz
Déborah
D
Bourc'his
D000818:Animals; D001755:Blastocyst / Q000378:metabolism; D015820:Cadherins / Q000235:genetics*; D019175:DNA Methylation; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism*; D005306:Fertilization; D005820:Genetic Testing; D018392:Genomic Imprinting; D005854:Germ Cells / Q000378:metabolism*; D051379:Mice; D009865:Oocytes / Q000378:metabolism*; D011544:Pseudogenes; D017422:Sequence Analysis, DNA
D015820:Cadherins; C070896:M-cadherin