Disruption of imprinted gene methylation and expression in cloned preimplantation stage mouse embryos

被引:251
作者
Mann, MRW
Chung, YG
Nolen, LD
Verona, RI
Latham, KE [1 ]
Bartolomei, MS
机构
[1] Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA
[2] Temple Univ, Sch Med, Dept Biochem, Philadelphia, PA 19140 USA
[3] Univ Penn, Sch Med, Howard Hughes Med Inst, Philadelphia, PA 19104 USA
[4] Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA
关键词
early development; embryo; gene regulation;
D O I
10.1095/biolreprod.103.017293
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cloning by somatic cell nuclear transfer requires that epigenetic information possessed by the donor nucleus be reprogrammed to an embryonic state. Little is known, however, about this remodeling process, including when it occurs, its efficiency, and how well epigenetic markings characteristic of normal development are maintained. Examining the fate of epigenetic information associated with imprinted genes during clonal development offers one means of addressing these questions. We examined transcript abundance, allele specificity of imprinted gene expression, and parental allele-specific DNA methylation in cloned mouse blastocysts. Striking disruptions were seen in total transcript abundance and allele specificity of expression for five imprinted genes. Only 4% of clones recapitulated a blastocyst mode of expression for all five genes. Cloned embryos also exhibited extensive loss of allele-specific DNA methylation at the imprinting control regions of the H19 and Snprn genes. Thus, epigenetic errors arise very early in clonal development in the majority of embryos, indicating that reprogramming is inefficient and that some epigenetic information may be lost.
引用
收藏
页码:902 / 914
页数:13
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