X inactivation in the mouse embryo deficient for Dnmt1: distinct effect of hypomethylation on imprinted and random X inactivation.
It has been suggested that DNA methylation plays a crucial role in genomic imprinting and X inactivation. Using DNA methyltransferase 1 (Dnmt1)-deficient mouse embryos carrying X-linked lacZ transgenes, we studied the effects of genomic demethylation on X inactivation. Based on the expression pattern of lacZ, the imprinted X inactivation in the visceral endoderm, a derivative of the extraembryonic lineage, was unaffected in Dnmt1 mutant embryos at the time other imprinted genes showed aberrant expression. Random X inactivation in the embryonic lineage of Dnmt1 mutant embryos, however, was unstable as a result of hypomethylation, causing reactivation of, at least, one lacZ transgene that had initially been repressed. Our results suggest that maintenance of imprinted X inactivation in the extraembryonic lineage can tolerate extensive demethylation while normal levels of methylation are required for stable maintenance of X inactivation in the embryonic lineage.
Sado
T
T
Cardiovascular Research Center, Cancer Center and Department of Medicine, Harvard Medical School, Massachusetts General Hospital-East, 149, 13th Street, Charlestown, Massachusetts 02129, USA.
Fenner
M H
MH
Tan
S S
SS
Tam
P
P
Shioda
T
T
Li
E
E
D000818:Animals; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D019175:DNA Methylation; D005314:Embryonic and Fetal Development / Q000235:genetics*; D004707:Endoderm / Q000502:physiology; D005260:Female; D018392:Genomic Imprinting; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012045:Regulatory Sequences, Nucleic Acid; D012727:Sex Characteristics; D012729:Sex Chromosome Aberrations; D014781:Viscera / Q000196:embryology; D014960:X Chromosome; D001616:beta-Galactosidase / Q000235:genetics
D006903:Hydroxymethylglutaryl CoA Reductases; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619381:Dnmt1 protein, mouse; D001616:beta-Galactosidase