DNA Methylation Errors in Cloned Mouse Sperm by Germ Line Barrier Evasion.
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.
Department of Bioscience, Tokyo University of Agriculture, Tokyo, Japan.
Tasuku
T
Koike
Department of Bioscience, Tokyo University of Agriculture, Tokyo, Japan.
Takuya
T
Wakai
Department of Bioscience, Tokyo University of Agriculture, Tokyo, Japan.
Yuko
Y
Jincho
Department of Bioscience, Tokyo University of Agriculture, Tokyo, Japan.
Akihiko
A
Sakashita
NODAI Genome Research Center, Tokyo University of Agriculture, Tokyo, Japan.
Hisato
H
Kobayashi
Department of Biotechnology, University of Yamanashi, Yamanashi, Japan.
Eiji
E
Mizutani
Department of Biotechnology, University of Yamanashi, Yamanashi, Japan.
Sayaka
S
Wakayama
Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Fumihito
F
Miura
Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Takashi
T
Ito
Department of Bioscience, Tokyo University of Agriculture, Tokyo, Japan tomohiro@nodai.ac.jp.
Tomohiro
T
Kono
D000818:Animals; D019976:Cloning, Organism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013094:Spermatozoa / Q000378:metabolism*
DNA methylation; cloning; epigenetics; sperm; transgenerational effect