Epigenetics in liver disease

Authors

  • Derek A. Mann

    Corresponding author
    1. Fibrosis Research Laboratories, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
    • Address reprint requests to: D.A. Mann, Ph.D., Fibrosis Research Laboratories, Institute of Cellular Medicine, 4th Floor, William Leech Building, Newcastle University, Newcastle upon Tyne NE24HH, UK. E-mail: derek.mann@newcastle.ac.uk

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  • Potential conflict of interest: Prof. Mann consults for and received grants from GlaxoSmithKline. He consults for Novartis and UCB.

  • The author is funded by the UK Medical Research Council (MR/K001949/1), National Institutes of Health NIAAA (U01AA018663), the Newcastle Biomedical Research Centre funded by NIHR and is in receipt of grant funding from GlaxoSmithKline.

Abstract

Epigenetics is a term that encompasses a variety of regulatory processes that are able to crosstalk in order to influence gene expression and cell phenotype in response to environmental cues. A deep understanding of epigenetics offers the potential for fresh insights into the basis for complex chronic diseases and improved diagnostic and prognostic tools. Moreover, as epigenetic modifications are highly plastic and responsive to the environment, there is much excitement around the theme of epigenetic therapeutics, including not only new drugs but also more informed patient advice on lifestyle choices and their impact on pathology. This review briefly explains the molecular nature of the individual regulatory process that constitute epigenetics, including DNA methylation, histone modifications, chromatin remodeling, transcriptional control, and noncoding RNAs. The ways in which these epigenetic mechanisms influence liver physiology and disease will be considered in detail, particularly in the context of cancer, fibrosis, and nonalcoholic steatohepatitis. The current limitations associated with epigenetic profiling and therapeutics in liver disease are discussed, as is the intriguing possibility that environmental-induced epigenetic changes may become stable and heritable. Conclusion: The aim of the review is to inform hepatologists of the emerging key epigenetic ideas of relevance to liver diseases that are highly likely to form a component of patient management and care in the next decade. (Hepatology 2014;60:1418–1425)

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