Figure 6.

A model for transgenerational epigenetic inheritance. We can consider a hypothetical allele that is marked at a single site by methylation (m). The silent phenotype corresponds to a methylated state, and the penetrant phenotype corresponds to the nonmethylated state. During gametogenesis (i), the marks escape demethylation, and therefore the overall epigenetic profile of the allele in mature sperm (five gametes shown for each male) correlates with the epigenetic state of the allele in somatic tissue of that animal. After fertilization (ii), the inability of the cell to erase marks at initially unmethylated alleles is inconsequential, but some alleles that were methylated initially will not be cleared completely. Ultimately, this will result in some memory of the epigenetic state of the parent's allele. This transgenerational epigenetic inheritance will not occur if the epigenetic marks are cleared completely postfertilization (not indicated in the figure), e.g., paternal copies of Axin^Fu and A^vy in the C57BL/6J-fertilized egg.