Human Molecular Genetics Advance Access originally published online on March 3, 2004
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Human Molecular Genetics, 2004, Vol. 13, No. 8 839-849
DOI: 10.1093/hmg/ddh104
Human Molecular Genetics, Vol. 13, No. 8 © Oxford University Press 2004; all rights reserved
Gene-specific timing and epigenetic memory in oocyte imprinting
1McGill University, Montreal Children's Hospital Research Institute and Departments of Pediatrics, Human Genetics, and Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada H3H 1P3 and 2Howard Hughes Medical Institute and Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Received December 15, 2003; Accepted February 18, 2004
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.
* To whom correspondence should be addressed at: McGill University, Montreal Children's Hospital Research Institute, 4060 Ste. Catherine Street West, Montreal, Quebec, Canada H3Z 2Z3. Tel: +1 5144124400, ext. 25235; Fax: +1 5144124331; Email: jacquetta.trasler{at}mcgill.ca
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