Abnormal regulation of DNA methyltransferase expression in cloned mouse embryos.
Cloning by somatic cell nuclear transfer is inefficient. This is evident in the significant attrition in the number of surviving cloned offspring at virtually all stages of embryonic and fetal development. We find that cloned preimplantation mouse embryos aberrantly express the somatic form of the Dnmt1 DNA (cytosine-5) methyltransferase, the expression of which is normally prevented by a posttranscriptional mechanism. Additionally, the maternal oocyte-derived Dnmt1o isoform undergoes little or none of its expected translocation to embryonic nuclei at the eight-cell stage. Such defects in the regulation of Dnmt1s and Dnmt1o expression and cytoplasmic-nuclear trafficking may prevent clones from completing essential early developmental events. Furthermore, aberrant Dnmt1 localization and expression may contribute to the defects in DNA methylation and the developmental abnormalities seen in cloned mammals.
Chung
Young Gie
YG
The Fels Institute for Cancer Research and Molecular Biology and Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Ratnam
Sarayu
S
Chaillet
J Richard
JR
Latham
Keith E
KE
D000818:Animals; D001755:Blastocyst / Q000201:enzymology*; D002467:Cell Nucleus / Q000201:enzymology; D002970:Cleavage Stage, Ovum / Q000201:enzymology; D019976:Cloning, Organism; D003593:Cytoplasm / Q000201:enzymology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009028:Morula / Q000201:enzymology; D009030:Mosaicism; D053652:Nuclear Transfer Techniques; D011247:Pregnancy
D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619381:Dnmt1 protein, mouse