Abstract
Environmental factors, particularly during early life, are important for the later metabolic health of the individual. In our obesogenic environment, it is of major socio-economic importance to investigate the mechanisms that contribute to the risk of metabolic ill health. Increasing evidence from a variety of model organisms suggests that non-genetically determined phenotypes, including metabolic effects such as glucose intolerance and obesity, can be passed between generations, which encourages us to revisit heredity. Inheritance of altered epigenetic information through the germ line has been proposed as one plausible mechanism. Whether the germline epigenome can be altered by environmental conditions such as diet and the extent to which this occurs in humans are the subject of intense current interest and debate, especially given that extensive germline epigenetic reprogramming is known to occur. As epigenetic mechanisms are often highly conserved between organisms, studying epigenetic inheritance in plants and lower metazoans has the potential to inform our investigation in mammals. This Review explores the extent to which epigenetic inheritance contributes to heredity in these different organisms, whether the environment can affect epigenetic inheritance and whether there is any evidence for the inheritance of acquired phenotypes.
Key points
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Epigenetic marks control cellular identity and gene expression and are inherited when a cell divides by mitosis.
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In mammals, we previously believed that all epigenetic marks are erased and reapplied (also termed reprogrammed) twice in a life cycle: once in the developing germ line and again in the early embryo.
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Regions that are resistant to this epigenetic reprogramming might facilitate the inheritance of environmentally conferred epigenetic information between generations.
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Epigenetic inheritance occurs in plants and animals such as the worm Caenorhabditis elegans, where less reprogramming of the marks occurs between generations.
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There is some evidence for epigenetic inheritance in small mammals such as mice, but the precise mechanisms involved are not yet well understood.
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At present, evidence for epigenetic inheritance in human populations is sparse, and it remains unclear to what extent epigenetic inheritance is important in human health and disease.
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The author thanks A. Ferguson-Smith for invaluable discussions and comments on the manuscript. The author apologizes to the authors of important original research papers whose work could not be cited owing to space restrictions.
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Radford, E.J. Exploring the extent and scope of epigenetic inheritance. Nat Rev Endocrinol 14, 345–355 (2018). https://doi.org/10.1038/s41574-018-0005-5
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DOI: https://doi.org/10.1038/s41574-018-0005-5
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