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Aberrant methylation of donor genome in cloned bovine embryos

Nature Genetics volume 28, pages 173–177 (2001)Cite this article

Abstract

Despite recent successes in cloning various animal species, the use of somatic cells as the source of donor nuclei has raised many practically relevant questions such as increased abortion rates, high birth weight and perinatal death1,2,3. These anomalies may be caused by incomplete epigenetic reprogramming of donor DNA. Genome-wide demethylation occurs during early development, 'erasing' gamete-specific methylation patterns inherited from the parents4,5,6,7,8. This process may be a prerequisite for the formation of pluripotent stem cells that are important for the later development9. Here, we provide evidence that cloned bovine embryos may have impaired epigenetic reprogramming capabilities. We found highly aberrant methylation patterns in various genomic regions of cloned embryos. Cloned blastocysts closely resembled donor cells in their overall genomic methylation status, which was very different from that of normal blastocysts produced in vitro or in vivo. We found demethylation of the Bov-B long interspersed nuclear element sequence in normal embryos, but not in cloned embryos, in which the donor-type methylation was simply maintained during preimplantation development. There were also significant variations in the degree of methylation among individual cloned blastocysts. Our findings indicate that the developmental anomalies of cloned embryos could be due to incomplete epigenetic reprogramming of donor genomic DNA.

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Figure 1: Methylation status of the satellite I sequences of fetal bovine fibroblasts in growing and starved conditions.
Figure 2: Methylation status of the satellite sequences of IVF or NT bovine embryos at various developmental stages.
Figure 3: Methylation status of individual blastocysts in the satellite I region.
Figure 4: Methylation of various genomic sequences in donor cells and IVF- or NT-derived blastocysts.
Figure 5: Changes in DNA methylation of the Bov-B long interspersed nuclear element repeats in embryos derived from IVF (a) or NT (b).

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Acknowledgements

We thank Y.I. Yeom for help, discussions and comments on the manuscript. We also thank H. Leonhardt and H.J. Hong for peer review and comments on the manuscript. This work is supported by grants (HS2705 and HS2550) of the Ministry of Science and Technology (MOST), Korea.

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  1. Animal Developmental Biotechnology Laboratory, Korea Research Institute of Bioscience and Biotechnology (KRIBB), PO Box 115, Yusong, 305-600, Taejon, South Korea

    Yong-Kook Kang, Deog-Bon Koo, Jung-Sun Park, Young-Hee Choi, Kyung-Kwang Lee & Yong-Mahn Han

  2. Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Taejon, 305-701, South Korea

    An-Sik Chung

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Kang, YK., Koo, DB., Park, JS. et al. Aberrant methylation of donor genome in cloned bovine embryos. Nat Genet 28, 173–177 (2001). https://doi.org/10.1038/88903

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