DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development.
The establishment of DNA methylation patterns requires de novo methylation that occurs predominantly during early development and gametogenesis in mice. Here we demonstrate that two recently identified DNA methyltransferases, Dnmt3a and Dnmt3b, are essential for de novo methylation and for mouse development. Inactivation of both genes by gene targeting blocks de novo methylation in ES cells and early embryos, but it has no effect on maintenance of imprinted methylation patterns. Dnmt3a and Dnmt3b also exhibit nonoverlapping functions in development, with Dnmt3b specifically required for methylation of centromeric minor satellite repeats. Mutations of human DNMT3B are found in ICF syndrome, a developmental defect characterized by hypomethylation of pericentromeric repeats. Our results indicate that both Dnmt3a and Dnmt3b function as de novo methyltransferases that play important roles in normal development and disease.
Okano
M
M
Cardiovascular Research Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, Charlestown 02129, USA.
Bell
D W
DW
Haber
D A
DA
Li
E
E
D000818:Animals; D001755:Blastocyst / Q000502:physiology*; D002503:Centromere / Q000235:genetics; D003433:Crosses, Genetic; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D006720:Homozygote; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics; D008297:Male; D008322:Mammals; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012091:Repetitive Sequences, Nucleic Acid; D013234:Stem Cells / Q000502:physiology; D000097584:DNA Methyltransferase 3B
D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C000715535:Dnmt3a protein, mouse