From correlation to causation: The new frontier of transgenerational epigenetic inheritance

While heredity is predominantly controlled by what deoxyribonucleic acid (DNA) sequences are passed from parents to their offspring, a small but growing number of traits have been shown to be regulated in part by the non-genetic inheritance of information. Transgenerational epigenetic inheritance is defined as heritable information passed from parents to their offspring without changing the DNA sequence. Work of the past seven decades has transitioned what was previously viewed as rare phenomenology, into well-established paradigms by which numerous traits can be modulated. For the most part, studies in model organisms have correlated transgenerational epigenetic inheritance phenotypes with changes in epigenetic modifications. The next steps for this field will entail transitioning from correlative studies to causal ones. Here, we delineate the major molecules that have been implicated in transgenerational epigenetic inheritance in both mammalian and non-mammalian models, speculate on additional molecules that could be involved, and highlight some of the tools which might help transition this field from correlation to causation.