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Biol Reprod. 2016 Jun;94(6):128. doi: 10.1095/biolreprod.116.138677. Epub 2016 Apr 20.

DNA Methylation Errors in Cloned Mouse Sperm by Germ Line Barrier Evasion.

Author information

1
Department of Bioscience, Tokyo University of Agriculture, Tokyo, Japan.
2
NODAI Genome Research Center, Tokyo University of Agriculture, Tokyo, Japan.
3
Department of Biotechnology, University of Yamanashi, Yamanashi, Japan.
4
Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
5
Department of Bioscience, Tokyo University of Agriculture, Tokyo, Japan tomohiro@nodai.ac.jp.

Abstract

The germ line reprogramming barrier resets parental epigenetic modifications according to sex, conferring totipotency to mammalian embryos upon fertilization. However, it is not known whether epigenetic errors are committed during germ line reprogramming that are then transmitted to germ cells, and consequently to offspring. We addressed this question in the present study by performing a genome-wide DNA methylation analysis using a target postbisulfite sequencing method in order to identify DNA methylation errors in cloned mouse sperm. The sperm genomes of two somatic cell-cloned mice (CL1 and CL7) contained significantly higher numbers of differentially methylated CpG sites (P = 0.0045 and P = 0.0116). As a result, they had higher numbers of differentially methylated CpG islands. However, there was no evidence that these sites were transmitted to the sperm genome of offspring. These results suggest that DNA methylation errors resulting from embryo cloning are transmitted to the sperm genome by evading the germ line reprogramming barrier.

KEYWORDS:

DNA methylation; cloning; epigenetics; sperm; transgenerational effect

PMID:
27103445
DOI:
10.1095/biolreprod.116.138677
[Indexed for MEDLINE]

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