Gene-specific timing and epigenetic memory in oocyte imprinting.
Imprinted genes are differentially marked during germ cell development to allow for their eventual parent-of-origin specific expression. A subset of imprinted genes becomes methylated during oocyte growth in both mouse and human. However the timing and mechanisms of methylation acquisition are unknown. Here, we examined the methylation of the Snrpn, Igf2r, Peg1 and Peg3 differentially methylated regions in postnatal growing mouse oocytes. Our findings indicate that methylation was acquired asynchronously at these different genes. Further analysis of Snrpn DMR1 revealed that parental alleles retain an epigenetic memory of their origin as the two alleles were recognized in a parental-specific manner in the absence of DNA methylation. In addition, we show that methylation acquisition was probably related to oocyte diameter and coincided with the accumulation of Dnmt3a, Dnmt3b and Dnmt3L transcripts. Methylation of the repetitive retroviral-like intracisternal A particle also occurred during this same window of oocyte growth. These findings contribute to our understanding of the epigenetic mechanisms underlying imprint acquisition during female germ cell development and have implications for the practice of assisted reproductive technologies.
McGill University, Montreal Children's Hospital Research Institute and Departments of Pediatrics, Human Genetics and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3H 1P3.
Diana
D
Lucifero
Mellissa R W
MR
Mann
Marisa S
MS
Bartolomei
Jacquetta M
JM
Trasler
D000818:Animals; D001324:Autoantigens; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D044127:Epigenesis, Genetic; D005260:Female; D007426:Genes, Intracisternal A-Particle / Q000502:physiology; D018392:Genomic Imprinting; D051379:Mice; D009865:Oocytes / Q000254:growth & development / Q000378:metabolism*; D017411:Ribonucleoproteins, Small Nuclear / Q000235:genetics / Q000378:metabolism; D020079:Terminal Repeat Sequences / Q000502:physiology; D013997:Time Factors; D055517:snRNP Core Proteins
D001324:Autoantigens; C000717967:DNMT3A protein, human; C000715535:Dnmt3a protein, mouse; D017411:Ribonucleoproteins, Small Nuclear; C526417:SNRPN protein, human; D055517:snRNP Core Proteins; C498796:Dnmt3l protein, mouse; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A