So in this part we’ll be looking at epigenetic inheritance- more precisely, the question of whether epigenetic marks, be they DNA methylation or histone modifications, are passed on from generation to generation. The relevant experimental model here
So in this part we’ll be looking at epigenetic inheritance- more precisely, the question of whether epigenetic marks, be they DNA methylation or histone modifications, are passed on from generation to generation. The relevant experimental model here is, unsurprisingly, the mouse.
We need to bring back the agouti gene mouse talked about in the last part. In an experiment done by Emma Whitelaw, it was seen that a yellow mother only gives birth to yellow or lightly colored pups, never a dark one; while a dark mother may give birth to some dark pups. As was discussed in part 4- this particular phenotypic variation is epigenetic, not genetic. It was because of a retrotransposon being methylated that the agouti gene’s expression was silenced (lack of methylation would mean constitutive expression). So the fact that a phenotypic variation caused by epigenetic mechanisms is heritable goes some distance to prove that epigenetic patterns are in fact inherited.
Well, there are a few more complexities. For any such mother-offspring non-DNA inheritance, there are three possible explanations:
- It could be due to DNA methylation and/or histone modification marks being inherited transgenerationally, which is what we’re interested in.
- It could be due to the intrauterine environment that the offspring comes to have those peculiar features. In this case, perhaps the agouti gene affects other aspects of the organism, which may include the environment where the fetus is developed, or specific modes in which the fetus gets nutrition, etc. In that case, it’s not really epigenetic marks that are being inherited, but the fetus is affected by the way the mother’s intrauterine environment is set up (which in turn may have been due to the agouti gene, or some environmental effect or other).
- It could be that the cytoplasmic environment that the fetus receives from the egg is what’s responsible. The mother passes on quite a bit of cytoplasm in her egg, so maybe that was shaped in a particular way by genetics or environment, which contributed to the fetus’ development.
To rule out (2) above, scientists took fertilized eggs from a yellow mother and implanted it into a dark one and got the same results, showing intrauterine environments weren’t responsible. Complex breeding schemes also ruled out (3), establishing firmly that DNA methylation in the case of agouti gene repression can indeed be inherited transgenerationally. Also, male-to-offspring inheritance of epigenetic m