DNA methyltransferase 1o functions during preimplantation development to preclude a profound level of epigenetic variation.
Most mouse embryos developing in the absence of the oocyte-derived DNA methyltransferase 1o (DNMT1o-deficient embryos) have significant delays in development and a wide range of anatomical abnormalities. To understand the timing and molecular basis of such variation, we studied pre- and post-implantation DNA methylation as a gauge of epigenetic variation among these embryos. DNMT1o-deficient embryos showed extensive differences in the levels of methylation in differentially methylated domains (DMDs) of imprinted genes at the 8-cell stage. Because of independent assortment of the methylated and unmethylated chromatids created by the loss of DNMT1o, the deficient embryos were found to be mosaics of cells with different, but stable epigenotypes (DNA methylation patterns). Our results suggest that loss of DNMT1o in just one cell cycle is responsible for the extensive variation in the epigenotypes in both embryos and their associated extraembryonic tissues. Thus, the maternal-effect DNMT1o protein is uniquely poised during development to normally ensure uniform parental methylation patterns at DMDs.
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
M Cecilia
MC
Cirio
Josee
J
Martel
Mellissa
M
Mann
Marc
M
Toppings
Marisa
M
Bartolomei
Jacquetta
J
Trasler
J Richard
JR
Chaillet
D000818:Animals; D002460:Cell Line; D002842:Chromatids / Q000235:genetics / Q000502:physiology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000502:physiology*; D019175:DNA Methylation / Q000502:physiology*; D010064:Embryo Implantation / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000235:genetics / Q000502:physiology*; D005260:Female; D018392:Genomic Imprinting / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009865:Oocytes / Q000378:metabolism; D010920:Placenta / Q000378:metabolism
D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619381:Dnmt1 protein, mouse