ACCESSION NO:  93-94-1708
       TITLE:  Role for DNA Methylation in Genomic Imprinting
      AUTHOR:  LI, EN; BEARD, CAROLINE; JAENISCH, RUDOLF
     JOURNAL:  Nature
    CITATION:  November 25, 1993, 366(6453): 362-365.
        YEAR:  1993
    PUB TYPE:  Article
 IDENTIFIERS:  GENETIC IMPRINTING; DNA METHYLATION; MOLECULAR BIOLOGY; 
               INHERITANCE
ABSTRACT: The paternal and maternal genomes are not equivalent and both are required for mammalian development. The difference between the parental genomes is believed to be due to gamete- specific differential modification, a process known a genomic imprinting. The study of transgene methylation has shown that methylation patterns can be inherited in a parent-of-origin- specific manner, suggesting that DNA methylation may play a role in genomic imprinting. The functional significance of DNA methylation in genomic imprinting was strengthened by the recent finding the CpG islands (or sites) in three imprinted genes, H19, insulin-like growth factor 2 (Igf-2), and Igf-2 receptor (Igf-2r), are differentially methylated depending on their parental origin.

A study was conducted to examine the expression of these three imprinted genes in mutant mice that are deficient in DNA methyltransferase activity. Results indicate that expression of all three genes was affected in mutant embryos: the normally silent paternal allele of the H19 gene was activated, whereas the normally active paternal allele of the Igf-2 gene and the active maternal allele of the Igf-2r gene were repressed. These results demonstrate that a normal level of DNA methylation is required for controlling differential expression of the paternal and maternal alleles of imprinted genes.