Conservation of methylation reprogramming in mammalian development: Aberrant reprogramming in cloned embryos

• Wendy Dean

  Laboratory of Developmental Genetics and Imprinting, Developmental Genetics Program, Babraham Institute, Cambridge CB2 4AT, United Kingdom; Institute of Molecular Animal Breeding, Gene Centre, Ludwig-Maximilian University, Munich, Germany; Max-Planck-Institut für Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; and Universität des Saarlandes, Genetik, 66041 Saarbrücken, Germany

• Fátima Santos

  Laboratory of Developmental Genetics and Imprinting, Developmental Genetics Program, Babraham Institute, Cambridge CB2 4AT, United Kingdom; Institute of Molecular Animal Breeding, Gene Centre, Ludwig-Maximilian University, Munich, Germany; Max-Planck-Institut für Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; and Universität des Saarlandes, Genetik, 66041 Saarbrücken, Germany

• Miodrag Stojkovic

  Laboratory of Developmental Genetics and Imprinting, Developmental Genetics Program, Babraham Institute, Cambridge CB2 4AT, United Kingdom; Institute of Molecular Animal Breeding, Gene Centre, Ludwig-Maximilian University, Munich, Germany; Max-Planck-Institut für Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; and Universität des Saarlandes, Genetik, 66041 Saarbrücken, Germany

• Valeri Zakhartchenko

  Laboratory of Developmental Genetics and Imprinting, Developmental Genetics Program, Babraham Institute, Cambridge CB2 4AT, United Kingdom; Institute of Molecular Animal Breeding, Gene Centre, Ludwig-Maximilian University, Munich, Germany; Max-Planck-Institut für Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; and Universität des Saarlandes, Genetik, 66041 Saarbrücken, Germany

• Jörn Walter

  Laboratory of Developmental Genetics and Imprinting, Developmental Genetics Program, Babraham Institute, Cambridge CB2 4AT, United Kingdom; Institute of Molecular Animal Breeding, Gene Centre, Ludwig-Maximilian University, Munich, Germany; Max-Planck-Institut für Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; and Universität des Saarlandes, Genetik, 66041 Saarbrücken, Germany

• Eckhard Wolf

  Laboratory of Developmental Genetics and Imprinting, Developmental Genetics Program, Babraham Institute, Cambridge CB2 4AT, United Kingdom; Institute of Molecular Animal Breeding, Gene Centre, Ludwig-Maximilian University, Munich, Germany; Max-Planck-Institut für Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; and Universität des Saarlandes, Genetik, 66041 Saarbrücken, Germany

• Wolf Reik

  Laboratory of Developmental Genetics and Imprinting, Developmental Genetics Program, Babraham Institute, Cambridge CB2 4AT, United Kingdom; Institute of Molecular Animal Breeding, Gene Centre, Ludwig-Maximilian University, Munich, Germany; Max-Planck-Institut für Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany; and Universität des Saarlandes, Genetik, 66041 Saarbrücken, Germany

抄録

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.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 98 (24), 13734-13738, 2001-11-20

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1361981471440886912
• NII論文ID: 80012880432
• DOI: 10.1073/pnas.241522698
• ISSN: 10916490
• ISSN: 00278424
• ISSN: http://id.crossref.org/issn/00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.241522698
• データソース種別:
  • Crossref
  • CiNii Articles