Abstracts (poster) - Wissenschaft Online

Jennifer Cropley, Catherine Suter, David Martin
A progressive multigenerational shift in epigenotype with
continuous methyl donor supplementation
The epigenetic state of a locus can be affected by environmental factors such as diet.
The murine A vy (agouti viable yellow) allele is one such locus: dietary supplementation
of pregnant dams with methyl donors changes the epigenetic state of the locus in the
offspring. At A vy , an IAP retrotransposon is inserted upstream of agouti. When
epigenetically active the IAP usurps transcriptional control, driving ectopic expression of
agouti signalling protein to produce the characteristic obese yellow phenotype. The
epigenetic state of the IAP is unstable in the germline, so that isogenic mice show wide
variation in the somatic epigenetic state of the IAP, with resultant broadly variable
penetrance and expressivity. Supplementation of maternal diet with methyl donors
promotes epigenetic silencing of the IAP, shifting the spectrum of offspring phenotypes
away from obese yellow. We have previously shown that methyl donors can affect the
germline epigenetic state of the A vy IAP. Here we show that continual supplementation
of A vy mice over five generations leads to progressive germline stabilisation of the IAP
epigenotype, so that the silent state becomes more strongly heritable and thus
significantly more prevalent in the population. In unsupplemented populations the IAP is
completely silent in 13% of mice. In a supplemented population, successive breeding of
males carrying a silent IAP increases the prevalence of the silent allele almost three-fold
(to 31%) by the fifth generation. These results suggest that long-term exposure to an
environmental stimulus can effect epigenetic changes throughout a population. Such
mechanisms may contribute to adaptive evolution via stable epigenetic silencing in the
germline.
contact:
Dr Jennifer Cropley
Victor Chang Cardiac Research Institute
j.cropley@victorchang.edu.au
384 Victoria st
2010 Darlinghurst (Australia)
additional information
Dr Catherine Suter: Victor Chang Cardiac Research Institute, Darlinghurst, Australia
Prof David Martin: Childrens Hospital Oakland Research Institute, Oakland, CA, USA