PT  - JOURNAL ARTICLE
AU  - LM Legault
AU  - K Doiron
AU  - A Lemieux
AU  - M Caron
AU  - D Chan
AU  - FL Lopes
AU  - G Bourque
AU  - D Sinnett
AU  - S McGraw
TI  - Developmental Genome-Wide DNA Methylation Asymmetry Between Mouse Placenta and Embryo
AID  - 10.1101/718247
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 718247
4099  - http://biorxiv.org/content/early/2019/08/05/718247.short
4100  - http://biorxiv.org/content/early/2019/08/05/718247.full
AB  - In early embryos, DNA methylation is remodelled to initiate the developmental program but for mostly unknown reasons, methylation marks are acquired unequally between embryonic and placental cells. To better understand this, we generated high-resolution DNA methylation maps of mouse mid-gestation (E10.5) embryo and placenta. We uncovered specific subtypes of differentially methylated regions (DMRs) that contribute directly to the developmental asymmetry existing between mid-gestation embryonic and placental DNA methylation patterns. We show that the asymmetry occurs rapidly during the acquisition of marks in the post-implanted conceptus (E3.5-E6.5), and that these patterns are long-lasting across subtypes of DMRs throughout prenatal development and in somatic tissues. We reveal that at the peri-implantation stages, the de novo methyltransferase activity of DNMT3B is the main driver of methylation marks on asymmetric DMRs, and that DNMT3B can largely compensate for lack of DNMT3A in the epiblast and extraembryonic ectoderm, whereas DNMT3A can only partially palliate in the absence of DNMT3B. However, as development progresses and as DNMT3A becomes the principal de novo methyltransferase, the compensatory DNA methylation mechanism of DNMT3B on DMRs becomes less effective.Summary statement The kinetics of asymmetric DNA methylation acquisition of embryoplacenta differentially methylated regions is not a stepwise process occurring in embryonic and extraembryonic lineages, but a prompt progression in the early post-implanted conceptus.