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Publication : Dynamic CpG island methylation landscape in oocytes and preimplantation embryos.

First Author  Smallwood SA Year  2011
Journal  Nat Genet Volume  43
Issue  8 Pages  811-4
PubMed ID  21706000 Mgi Jnum  J:176177
Mgi Id  MGI:5288579 Doi  10.1038/ng.864
Citation  Smallwood SA, et al. (2011) Dynamic CpG island methylation landscape in oocytes and preimplantation embryos. Nat Genet 43(8):811-4
abstractText  Elucidating how and to what extent CpG islands (CGIs) are methylated in germ cells is essential to understand genomic imprinting and epigenetic reprogramming. Here we present, to our knowledge, the first integrated epigenomic analysis of mammalian oocytes, identifying over a thousand CGIs methylated in mature oocytes. We show that these CGIs depend on DNMT3A and DNMT3L but are not distinct at the sequence level, including in CpG periodicity. They are preferentially located within active transcription units and are relatively depleted in H3K4me3, supporting a general transcription-dependent mechanism of methylation. Very few methylated CGIs are fully protected from post-fertilization reprogramming but, notably, the majority show incomplete demethylation in embryonic day (E) 3.5 blastocysts. Our study shows that CGI methylation in gametes is not entirely related to genomic imprinting but is a strong factor in determining methylation status in preimplantation embryos, suggesting a need to reassess mechanisms of post-fertilization demethylation.
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