RECORD NO.:  94067323
       AUTHOR:  Li E; Beard C; Jaenisch R
      ADDRESS:  Whitehead Institute for Biomedical Research, Massachusetts 
                Institute of Technology, Cambridge 02142.
        TITLE:  Role for DNA methylation in genomic imprinting [see 
                comments]
       SOURCE:  Nature (NSC), 1993 Nov 25; 366 (6453): 362-5
     LANGUAGE:  English
 COUNTRY PUB.:  ENGLAND
 ANNOUNCEMENT:  9403
    PUB. TYPE:  JOURNAL ARTICLE
     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 as 
                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 that 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. We have examined the expression of these three 
                imprinted genes in mutant mice that are deficient in DNA 
                methyltransferase activity. We report here 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. Our results demonstrate that a normal 
                level of DNA methylation is required for controlling 
                differential expression of the paternal and maternal alleles 
                of imprinted genes.
        NOTES:  Comment in: Nature, 1993 Nov 25;366(6453):302-3
MESH HEADINGS:  DNA--metabolism (*ME); Fetal Development--genetics (*GE); 
                *Gene Expression Regulation; Alleles; DNA Modification 
                Methylases--genetics (GE); Homozygote; Methylation; Mice; 
                Mice, Mutant Strains; Parents; Animal; Female; Male; 
                Support, U.S. Gov't, P.H.S.
  GENE SYMBOL:  H19; Igf-2; Igf-2r; MTase
CHEMICAL SUBS:  EC 2.1.1.- (DNA Modification Methylases); 9007-49-2 (DNA)
 STANDARD NO.:  0028-0836
        DATES:  Entered 931230