ACCESSION NO:  93-94-1716
       TITLE:  Embryo Uses Chemistry to Tell Genes Apart
      AUTHOR:  STROBEL, GABRIELLE
     JOURNAL:  Science News
    CITATION:  November 27, 1993, 144(22): 357.
        YEAR:  1993
    PUB TYPE:  Article
 IDENTIFIERS:  GENETIC IMPRINTING; DNA METHYLATION; GENE SUPPRESSION; EMBRYO 
               GENE SELECTION; CHEMISTRY
ABSTRACT: When male and female germ cells unite to create a new life, their genetic contributions come with tags labeling them as maternal or paternal. "Reading" these tags, the developing embryo selects either the mother's or father's gene for expression, while leaving the other idle. Activating both parental genes, or neither, can cause fetal death or a serious disorder. Now, researchers report that this discrimination, called genetic imprinting, relies on a chemical mechanism. Methylation, the addition of molecules called methyl groups to the DNA molecule, is crucial for enabling the embryo to tell the parents' genes apart. Scientists had suspected that since methylation is an inherent DNA modification, it might help genes "remember" their origin; yet no one had ever directly linked the two.

The new evidence comes from knockout mice, animals altered to disrupt the gene for the DNA methylation enzyme. Analyzing three genes, the researchers found that in mutant embryos the parental imprints were erased. Moreover, mutant embryos didn't follow the normal pattern of activating only one parent's copy of a gene. According to the researchers, it appeared as if the embryo could not distinguish which gene came from which parent. This finding fit nicely with an assumption about DNA imprinting: that methylation represented a way to inhibit a gene. This was the case for one of the genes analyzed. The other two showed the opposite behavior: The mutation silenced the normally active gene. The researchers interpret this to mean that methylation activates some imprinted genes but inhibits others.

Adding another twist is the finding that DNA methylation seems to act on some genes directly but used genetic go- betweens--called gene silencers--to act on others. It is speculated that, depending on their methylation status, these silencers could determine the fate of imprinted genes.

A researcher also notes that not all genes are equally sensitive to the loss of DNA methylation. The imprint of certain genes vanished only in embryos in which methylation was almost entirely prevented. Less severely mutated embryos might rally their remaining methylation capacity to secure adequate methylation for a gene at the expense of others.