Molecular Genetics

Facts

A female mouse (circle) heterozygous for a transgene (black half of circle) was bred with a wild type male (square). Breeding was continued for several generations as indicated at right. The DNA of transgene-positive individuals was analyzed by restriction with HpaII, a CG methylation sensitive enzyme, gel electrophoresis and Southern blotting. The blot was probed by hybridization with the labeled transgene DNA. Single bands of either 5.6 or 1.8 kbp were detected (see right).

Interpretations

• Band size correlates with the sex of the transgene parent. When the transgene parent was the father, the DNA was undermethylated. When the transgene parent was the mother, the DNA was methylated.
• In spermatogenesis, methylation may be inhibited.
• Paternal imprinting may be due to methylation.

Further information

• A select few normal (nontransgenic) genes are also imprinted.
• The evolution of DNA methylation and its function in genomes is complex.
• Evidence from embryonic mouse cells lacking the DNA methyltransferase suggests that methylation protects the genome against deletions resulting from inappropriate recombination (press release).
• One mechanism by which methylation contributes to parental imprinting is the inactivation of insulators by methylation.
• Alternatively, methylation may just be an indicator of a heritable chromosomal state.
• Imprinted methylation patterns are not established during gametogenesis, but very soon after fertilization.
• Imprinting is one kind of epigenetic mechanism.
• Genome comparisons suggest that mammalian imprinting may have arisen due to certain mobile elements having integrated in regions that have become susceptible to imprinting (ref).

This is page 1382 of Molecular Genetics by Ulrich Melcher, © 1997-9, 2001, 2003, 2008