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Escape from epigenetic silencing of lactase expression is triggered by a single-nucleotide change

Nature Structural & Molecular Biology volume 23, pages 505–507 (2016)Cite this article

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The importance of subtle gene regulation and epigenetics in determining complex human traits is increasingly being recognized. However, bridging the gaps between environmental, epigenetic and genetic influences and unraveling causal relationships remain a big challenge. A study now reports an example of epigenetic changes influenced by genetic factors that are involved in the regulation of lactase gene expression.

Intestinal lactase is required for the digestion of lactose, the major carbohydrate in mammalian milk, but lactase gene expression is usually downregulated after weaning. In many humans, however, lactase persists into adult life, thus allowing digestion of milk and representing an evolutionary adaptation to dietary change. Decreased intestinal lactase levels—whether arising from developmental downregulation or secondary loss, such as that caused by enteritis—result in incomplete digestion of lactose. This incomplete digestion can lead to symptoms of diarrhea and flatulence after consumption of fresh milk. However, people who are lactase nonpersistent do not necessarily suffer from symptomatic lactose intolerance, because there are large interindividual differences in variables such as the gut-microbiome composition and gut transit time, as well as sensitivity to the symptoms.

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Figure 1: Inverse relationship between MCM6 and LCT enhancer methylation and lactase gene expression.

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Authors and Affiliations

  1. Dallas M. Swallow is at the Research Department of Genetics, Evolution and Environment, University College London, London, UK.,

    Dallas M Swallow

  2. Jesper T. Troelsen is at the Department of Science and Environment (INM), Roskilde University, Roskilde, Denmark.,

    Jesper T Troelsen

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  1. Dallas M Swallow
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Correspondence to Dallas M Swallow.

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Swallow, D., Troelsen, J. Escape from epigenetic silencing of lactase expression is triggered by a single-nucleotide change. Nat Struct Mol Biol 23, 505–507 (2016). https://doi.org/10.1038/nsmb.3238

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