Transgenerational Germ-line Epigenetic Modification with Nutritional Supplementation

The paper titled “Germ-line epigenetic modification of the murine A^vy allele by nutritional supplementation,” by Cropley et al. was considered to be the “most memorable epigenetic moment of the year” for 2006.It was a groundbreaking paper which published in Proceedings of the National Academy of Science in November (Cropley et al. 2006) because this paper provides the first direct evidence of a mechanism in a transgenerational, epigenetic alteration.

Cropley uses a mutant mouse strain known as viable yellow agouti, or A^vy. . As previous studies shown, mice carrying the viable yellow agouti allele exhibit yellow fur, obesity, type II diabetes, and predisposition to tumors. The epigenotype of the Avy allele is partially stable in the female germline, which lead to weak inheritance of the maternal phenotype. However, the phenotype of offspring is not influence by paternal A^vy epigenotype. Methyl donors would be more likely to alter the epigenotype of A^vy stably in the female germ line. In other words, nutritional supplementation during gestation seemed to cause an epigenetic alteration in phenotypes of offspring.

The germ-line alteration of the Avy epigenotype is definite evidence that an environmental factor can produce a phenotypic effect by inducing an epigenetic modification in the mammalian germ line, and that such a modification can persist through the epigenetic resetting that takes place during gametogenesis and embryogenesis. However, it would be interesting to see if the shift to the agouti phenotype would continue into the F3 and F4 generations, as would be expected if the epigenetic germ line was permanently reprogrammed.

Guo REN

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