X inactivation in the mouse embryo deficient for Dnmt1: distinct effect of hypomethylation on imprinted and random X inactivation

Dev Biol. 2000 Sep 15;225(2):294-303. doi: 10.1006/dbio.2000.9823.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / deficiency
  • DNA (Cytosine-5-)-Methyltransferases / genetics*
  • DNA (Cytosine-5-)-Methyltransferases / metabolism*
  • DNA Methylation
  • Embryonic and Fetal Development / genetics*
  • Endoderm / physiology
  • Female
  • Genomic Imprinting
  • Hydroxymethylglutaryl CoA Reductases / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Regulatory Sequences, Nucleic Acid
  • Sex Characteristics
  • Sex Chromosome Aberrations
  • Viscera / embryology
  • X Chromosome*
  • beta-Galactosidase / genetics


  • Hydroxymethylglutaryl CoA Reductases
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • Dnmt1 protein, mouse
  • beta-Galactosidase