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Dean, W. et al. Conservation of methylation reprogramming in mammalian development: aberrant reprogramming in cloned embryos. Proc. Natl Acad. Sci. USA 98, 13734-13738

Laboratory of Developmental Genetics and Imprinting, Developmental Genetics Program, Babraham Institute, Cambridge CB2 4AT, United Kingdom.
Proceedings of the National Academy of Sciences (Impact Factor: 9.81). 12/2001; 98(24):13734-8. DOI: 10.1073/pnas.241522698
Source: PubMed

ABSTRACT Mouse embryos undergo genome-wide methylation reprogramming by demethylation in early preimplantation development, followed by remethylation thereafter. Here we show that genome-wide reprogramming is conserved in several mammalian species and ask whether it also occurs in embryos cloned with the use of highly methylated somatic donor nuclei. Normal bovine, rat, and pig zygotes showed a demethylated paternal genome, suggesting active demethylation. In bovine embryos methylation was further reduced during cleavage up to the eight-cell stage, and this reduction in methylation was followed by de novo methylation by the 16-cell stage. In cloned one-cell embryos there was a reduction in methylation consistent with active demethylation, but no further demethylation occurred subsequently. Instead, de novo methylation and nuclear reorganization of methylation patterns resembling those of differentiated cells occurred precociously in many cloned embryos. Cloned, but not normal, morulae had highly methylated nuclei in all blastomeres that resembled those of the fibroblast donor cells. Our study shows that epigenetic reprogramming occurs aberrantly in most cloned embryos; incomplete reprogramming may contribute to the low efficiency of cloning.

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    • "al growing oocyte ( Hiura et al . , 2006 ; O &apos; Doherty et al . , 2012 ) . Following fertilization there is a global cascade of DNA demethylation during the early stages of embryogenesis , whereby the paternal genome is rapidly demethylated in the zygote and the maternal genome is passively demethy - lated in a replication - dependent manner ( Dean et al . , 2001 ; Yang et al . , 2007 ; Iqbal et al . , 2011 ) . More recently , it has been hypothesized that both the maternal and paternal genomes undergo global active demethylation and replication - mediated passive demethylation ( Gkountela and Clark , 2014 ; Guo et al . , 2014 ) . Irrespective of the mechanisms con - trolling these genome - wide"
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    • "This points to a more moderate rate or a delay in demethylation induced by oxidative stress. A similar trend was found in cloned bovine embryos (Bourc&apos;his et al. 2001; Dean et al. 2001). Conversely, higher "
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