Using epigenomics to understand cellular responses to environmental influences in diseases.

It is a generally accepted model that environmental influences can exert their effects, at least in part, by changing the molecular regulators of transcription that are described as epigenetic. As there is biochemical evidence that some epigenetic regulators of transcription can maintain their states long term and through cell division, an epigenetic model encompasses the idea of maintenance of the effect of an exposure long after it is no longer present. The evidence supporting this model is mostly from the observation of alterations of molecular regulators of transcription following exposures. With the understanding that the interpretation of these associations is more complex than originally recognised, this model may be oversimplistic; therefore, adopting novel perspectives and experimental approaches when examining how environmental exposures are linked to phenotypes may prove worthwhile. In this review, we have chosen to use the example of nonalcoholic fatty liver disease (NAFLD), a common, complex human disease with strong environmental and genetic influences. We describe how epigenomic approaches combined with emerging functional genetic and single-cell genomic techniques are poised to generate new insights into the pathogenesis of environmentally influenced human disease phenotypes exemplified by NAFLD.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JJW receives grant and contract funding from Galectin, Intercept, Genfit, Janssen, Shire, Conatus, Zydus, and Perspectum; she has served on advisory boards for Astra Zeneca/ MedImmune and AMRA. SR, DAK and JMG declare no conflicts. JMG, SR and DAK declare no conflicts.
(Copyright: © 2023 Wattacheril et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)